MEpedia - User contributions [en]

Ischemic Cascade

2024-05-12T14:28:44Z

Christopherd:Pinpointed Glutamate Excitoxicity as the likely cause of non-restorative sleep

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article provide a theory that maysimplify the pathophysiology of CFS/ME symptoms by classifying it under an already-established medical condition called Ischemic Cascade. Ischemic Cascade (IC) is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain being discussed, in response to a local condition of hypoxia.

Hypoxia appears to be the key issue in lack of exertion endurance in both skeletal muscle, and in the cognitive brain. Anecdotal reports have added that lowered emotional tolerance can precede or follow fatigue and "brain fog" in CFS/ME; that any one of the 3 areas of function can bring down either or both of the other two in a situation of exertion intolerance. This is evidence that CFS/ME is not about a single pathogen, and is not about a single tissue. RATHER, as shown in the 2019 SARS-COV2 pandemic and sequelae, this condition can arise from various types of insults to the human body but with the same types of results in the same body systems as seen in CFS/ME and in other autoimmune syndromes.

Leading theory on the subject of Long-Covid sequelae indicates that blood vessel dysfunction, specifically endothelial cell dysfunction, is the key weak link in the otherwise healthy body system. But the blood vessels: capillary, vein, artery, become compromised by systemic infection and SYSTEM-WIDE deficiency. What is NOT much discussed is the possible cause of MODS, multiple organ dsyfunction syndrome which is resulting often in Long-Covid. The possible cause postulated in this theory is attack of all smooth muscle organs, not limited to blood vessels, since common receptors preferred by some viruses exist in both areas.

The reason for the scrutiny of this article on the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis/ SEID is that this Cascade of responses appears to have been delineated as a local condition in mainstream medicine, and most often as a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome which as yet has no explained pathology.

Since SEID is a system-wide intolerance to exertion, and since the IC phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel damage and system-wide organ damage caused by Covid19 or by previous Influenza pandemics, and even triggered by patient-specific bacterial infections and weakened immune system function, may already have been defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae. If so, the definition of Ischemic Cascade may lead to the most direct intervention in ceasing the ME/CFS/SEID/Long-Covid obstacle to health.

The following standards are known to the author of this article: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease was established and adopted AFTER the previously mentioned disease monikers for the same condition.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies and furthermore overlooked in research as to their mitigation. The key clue that repeating IC may be the condition observed in CFS/ME/SEID is that there is non-restorative sleep with an as-yet unknown cause. The component in IC which can account for hyper-arousal during sleep and prevention of adequate delta phase sleep is an initial Glutamate Excitotoxicity and some amount of feedback sometimes leading to additional Glutamate release outside affected cells.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been redacted by the medical community from the original mandatory 10 symptoms

POTS, or Postural Orthostatic Tachycardia Syndrome is the official name for such orthostatic intolerance.

What do ME/CFS/SEID/Long-Covid/POTS have in common?

INTOLERANCE.

And intolerance is a breach of homeostatic recovery.

NOTABLY: the key causative problem in MECFSSEIDLONGCOVID is:

a continued inflammation from a continued pathogen insult, long after the main infection has ceased.

Lastly, before describling the ISCHEMIC CASCADE stages, it is fitting to make a plausible reference

to latent viruses which can be reactivated in cells throughout the course of one's life,

putatatively because they evaded the patient's immune reaction and also eradication by

novel antibodies.

THE ISCHEMIC CASCADE of EVENTS in response to Hypoxia:

NOTE: You are free to attempt to read the PubMed explanation of Ischemic Cascade, at your own personal cost.

However, the following is quoted from Wikipedia [[Ischemic cascade|Ischemic cascade - Wikipedia]]<ref>{{Cite journal|title=Ischemic cascade|date=2024-02-09|url=https://en.wikipedia.org/w/index.php?title=Ischemic_cascade&oldid=1205244473|journal=Wikipedia|language=en}}</ref>

== "Mechanism ==
A [[Biochemical cascade|cascade]] is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events. In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:[''[[Wikipedia:Citation needed|citation needed]]'']

# Low blood supply decreases amount of oxygen that reaches tissues, leading to [[Hypoxia (medical)|hypoxia]]
# Deficiency of oxygen causes the neuron's normal process for making [[Adenosine triphosphate|ATP]] for energy to fail.
# The cell switches to [[Fermentation (biochemistry)|anaerobic metabolism]], producing [[lactic acid]].
# ATP-reliant [[Ion pump (biology)|ion transport pumps]] fail, causing the cell to become [[Action potential|depolarized]], allowing [[Ion|ions]], including [[calcium]] (Ca2+), to flow into the [[Cell (biology)|cell]].
# The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
# The presence of calcium triggers the release of the excitatory [[amino acid]] [[neurotransmitter]] [[glutamate]].
# Glutamate stimulates [[AMPA receptor|AMPA receptors]] and Ca2+-permeable [[NMDA receptor|NMDA receptors]], which open to allow more calcium into cells.
# Excess calcium entry overexcites cells and causes the generation of harmful chemicals like [[Free radical|free radicals]], [[reactive oxygen species]] and calcium-dependent [[Enzyme|enzymes]] such as [[calpain]], [[Endonuclease|endonucleases]], [[ATPase|ATPases]], and [[Phospholipase|phospholipases]] in a process called [[excitotoxicity]]. Calcium can also cause the release of more glutamate.
# As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.
# [[Mitochondrion|Mitochondria]] break down, releasing toxins and [[Apoptosis|apoptotic]] factors into the cell.
# The [[caspase]]-dependent [[apoptosis]] cascade is initiated, causing cells to "commit suicide."
# If the cell dies through [[necrosis]], it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby [[Neuron|neurons]], and glutamate can overexcite them.
# If and when the brain is reperfused, a number of factors lead to [[reperfusion injury]].
# An [[Inflammation|inflammatory]] response is mounted, and [[Phagocytosis|phagocytic]] cells engulf damaged but still viable tissue.
# Harmful chemicals damage the [[blood–brain barrier]].
# [[Cerebral edema]] (swelling of the brain) occurs due to leakage of large [[Molecule|molecules]] like [[albumins]] from blood vessels through the damaged [[blood brain barrier]]. These large molecules pull water into the brain tissue after them by [[osmosis]]. This "[[vasogenic edema]]" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases)."" ([[Ischemic cascade|Ischemic cascade - Wikipedia]])

The CRUCIAL elements of Ischemic Cascade are:

# this was only considered to be local, such as in the brain or a damaged area: conside this as as SYSTEM-WIDE reaction to system-wide hypoxia and endothelial cell damage as result of Influenza infection via Sialic Acid receptors, and also coronavirus infection by Covid19 via ACE2 receptors.
# NOTE: ACE2 receptor means: Angitension Converting Enzyme receptor with the purpose of converting Angiotensin II vasoconstrictor to Angiotensions 1-7 of which one is a vasodilator, and a trigger of NADPH antioxidant flourishing in the Krebs Cycle. 

__INDEX__
__NEWSECTIONLINK__

Ischemic Cascade

2024-05-12T14:06:07Z

Christopherd:added the possible cause of MODS in the paragraph where first mentioned

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article provide a theory that maysimplify the pathophysiology of CFS/ME symptoms by classifying it under an already-established medical condition called Ischemic Cascade. Ischemic Cascade (IC) is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain being discussed, in response to a local condition of hypoxia.

Hypoxia appears to be the key issue in lack of exertion endurance in both skeletal muscle, and in the cognitive brain. Anecdotal reports have added that lowered emotional tolerance can precede or follow fatigue and "brain fog" in CFS/ME; that any one of the 3 areas of function can bring down either or both of the other two in a situation of exertion intolerance. This is evidence that CFS/ME is not about a single pathogen, and is not about a single tissue. RATHER, as shown in the 2019 SARS-COV2 pandemic and sequelae, this condition can arise from various types of insults to the human body but with the same types of results in the same body systems as seen in CFS/ME and in other autoimmune syndromes.

Leading theory on the subject of Long-Covid sequelae indicates that blood vessel dysfunction, specifically endothelial cell dysfunction, is the key weak link in the otherwise healthy body system. But the blood vessels: capillary, vein, artery, become compromised by systemic infection and SYSTEM-WIDE deficiency. What is NOT much discussed is the possible cause of MODS, multiple organ dsyfunction syndrome which is resulting often in Long-Covid. The possible cause postulated in this theory is attack of all smooth muscle organs, not limited to blood vessels, since common receptors preferred by some viruses exist in both areas.

The reason for the scrutiny of this article on the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis/ SEID is that this Cascade of responses appears to have been delineated as a local condition in mainstream medicine, and most often as a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel damage and system-wide organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and weakened immune system function, may already have been defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae. If so, the definition of Ischemic Cascade may lead to the most direct intervention in ceasing the ME/CFS/SEID/Long-Covid obstacle to health.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease was established and adopted AFTER the previously mentioned disease monikers for the same condition.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies and furthermore overlooked in research as to their mitigation.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been redacted from the original mandatory 10 symptoms

POTS, or Postural Orthostatic Tachycardia Syndrome is the official name for such orthostatic intolerance.

What do ME/CFS/SEID/Long-Covid/POTS have in common?

INTOLERANCE.

And intolerance is a breach of homeostatic recovery.

NOTABLY: the key causative problem in MECFSSEIDLONGCOVID is:

a continued inflammation from a continued pathogen insult, long after the main infection has ceased.

Lastly, before describling the ISCHEMIC CASCADE stages, it is fitting to make a plausible reference

to latent viruses which can be reactivated in cells throughout the course of one's life,

putatatively because they evaded the patient's immune reaction and also eradication by

novel antibodies.

THE ISCHEMIC CASCADE of EVENTS in response to Hypoxia:

NOTE: You are free to attempt to read the PubMed explanation of Ischemic Cascade, at your own personal cost.

However, the following is quoted from Wikipedia [[Ischemic cascade|Ischemic cascade - Wikipedia]]<ref>{{Cite journal|title=Ischemic cascade|date=2024-02-09|url=https://en.wikipedia.org/w/index.php?title=Ischemic_cascade&oldid=1205244473|journal=Wikipedia|language=en}}</ref>

== "Mechanism ==
A [[Biochemical cascade|cascade]] is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events. In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:[''[[Wikipedia:Citation needed|citation needed]]'']

# Low blood supply decreases amount of oxygen that reaches tissues, leading to [[Hypoxia (medical)|hypoxia]]
# Deficiency of oxygen causes the neuron's normal process for making [[Adenosine triphosphate|ATP]] for energy to fail.
# The cell switches to [[Fermentation (biochemistry)|anaerobic metabolism]], producing [[lactic acid]].
# ATP-reliant [[Ion pump (biology)|ion transport pumps]] fail, causing the cell to become [[Action potential|depolarized]], allowing [[Ion|ions]], including [[calcium]] (Ca2+), to flow into the [[Cell (biology)|cell]].
# The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
# The presence of calcium triggers the release of the excitatory [[amino acid]] [[neurotransmitter]] [[glutamate]].
# Glutamate stimulates [[AMPA receptor|AMPA receptors]] and Ca2+-permeable [[NMDA receptor|NMDA receptors]], which open to allow more calcium into cells.
# Excess calcium entry overexcites cells and causes the generation of harmful chemicals like [[Free radical|free radicals]], [[reactive oxygen species]] and calcium-dependent [[Enzyme|enzymes]] such as [[calpain]], [[Endonuclease|endonucleases]], [[ATPase|ATPases]], and [[Phospholipase|phospholipases]] in a process called [[excitotoxicity]]. Calcium can also cause the release of more glutamate.
# As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.
# [[Mitochondrion|Mitochondria]] break down, releasing toxins and [[Apoptosis|apoptotic]] factors into the cell.
# The [[caspase]]-dependent [[apoptosis]] cascade is initiated, causing cells to "commit suicide."
# If the cell dies through [[necrosis]], it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby [[Neuron|neurons]], and glutamate can overexcite them.
# If and when the brain is reperfused, a number of factors lead to [[reperfusion injury]].
# An [[Inflammation|inflammatory]] response is mounted, and [[Phagocytosis|phagocytic]] cells engulf damaged but still viable tissue.
# Harmful chemicals damage the [[blood–brain barrier]].
# [[Cerebral edema]] (swelling of the brain) occurs due to leakage of large [[Molecule|molecules]] like [[albumins]] from blood vessels through the damaged [[blood brain barrier]]. These large molecules pull water into the brain tissue after them by [[osmosis]]. This "[[vasogenic edema]]" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases)."" ([[Ischemic cascade|Ischemic cascade - Wikipedia]])

The CRUCIAL elements of Ischemic Cascade are:

# this was only considered to be local, such as in the brain or a damaged area: conside this as as SYSTEM-WIDE reaction to system-wide hypoxia and endothelial cell damage as result of Influenza infection via Sialic Acid receptors, and also coronavirus infection by Covid19 via ACE2 receptors.
# NOTE: ACE2 receptor means: Angitension Converting Enzyme receptor with the purpose of converting Angiotensin II vasoconstrictor to Angiotensions 1-7 of which one is a vasodilator, and a trigger of NADPH antioxidant flourishing in the Krebs Cycle. 

__INDEX__
__NEWSECTIONLINK__

Ischemic Cascade

2024-05-12T14:00:10Z

Christopherd:improved grammar in first paragraph

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article provide a theory that maysimplify the pathophysiology of CFS/ME symptoms by classifying it under an already-established medical condition called Ischemic Cascade. Ischemic Cascade (IC) is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain being discussed, in response to a local condition of hypoxia.

Hypoxia appears to be the key issue in lack of exertion endurance in both skeletal muscle, and in the cognitive brain. Anecdotal reports have added that lowered emotional tolerance can precede or follow fatigue and "brain fog" in CFS/ME; that any one of the 3 areas of function can bring down either or both of the other two in a situation of exertion intolerance. This is further evidence that CFS/ME is not about a single pathogen, and is not about a single tissue. RATHER, as shown in the 2019 SARS-COV2 pandemic and sequelae, this condition can arise from various insults to the immune system but with the same result in the same systems.

Leading theory on the subject of Long-Covid sequelae indicates that blood vessel dysfunction, specifically endothelial cell dysfunction, is the key weak link in the otherwise healthy body system. But the blood vessels: capillary, vein, artery, become compromised by systemic infection and SYSTEM-WIDE deficiency. What is NOT much discussed is the possible cause of MODS, multiple organ dsyfunction syndrome which is resulting often in Long-Covid.

The reason for the scrutiny of this article on the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis/ SEID is that this Cascade of responses appears to have been delineated as a local condition in mainstream medicine, and most often as a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel damage and system-wide organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and weakened immune system function, may already have been defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae. If so, the definition of Ischemic Cascade may lead to the most direct intervention in ceasing the ME/CFS/SEID/Long-Covid obstacle to health.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease was established and adopted AFTER the previously mentioned disease monikers for the same condition.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies and furthermore overlooked in research as to their mitigation.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been redacted from the original mandatory 10 symptoms

POTS, or Postural Orthostatic Tachycardia Syndrome is the official name for such orthostatic intolerance.

What do ME/CFS/SEID/Long-Covid/POTS have in common?

INTOLERANCE.

And intolerance is a breach of homeostatic recovery.

NOTABLY: the key causative problem in MECFSSEIDLONGCOVID is:

a continued inflammation from a continued pathogen insult, long after the main infection has ceased.

Lastly, before describling the ISCHEMIC CASCADE stages, it is fitting to make a plausible reference

to latent viruses which can be reactivated in cells throughout the course of one's life,

putatatively because they evaded the patient's immune reaction and also eradication by

novel antibodies.

THE ISCHEMIC CASCADE of EVENTS in response to Hypoxia:

NOTE: You are free to attempt to read the PubMed explanation of Ischemic Cascade, at your own personal cost.

However, the following is quoted from Wikipedia [[Ischemic cascade|Ischemic cascade - Wikipedia]]<ref>{{Cite journal|title=Ischemic cascade|date=2024-02-09|url=https://en.wikipedia.org/w/index.php?title=Ischemic_cascade&oldid=1205244473|journal=Wikipedia|language=en}}</ref>

== "Mechanism ==
A [[Biochemical cascade|cascade]] is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events. In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:[''[[Wikipedia:Citation needed|citation needed]]'']

# Low blood supply decreases amount of oxygen that reaches tissues, leading to [[Hypoxia (medical)|hypoxia]]
# Deficiency of oxygen causes the neuron's normal process for making [[Adenosine triphosphate|ATP]] for energy to fail.
# The cell switches to [[Fermentation (biochemistry)|anaerobic metabolism]], producing [[lactic acid]].
# ATP-reliant [[Ion pump (biology)|ion transport pumps]] fail, causing the cell to become [[Action potential|depolarized]], allowing [[Ion|ions]], including [[calcium]] (Ca2+), to flow into the [[Cell (biology)|cell]].
# The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
# The presence of calcium triggers the release of the excitatory [[amino acid]] [[neurotransmitter]] [[glutamate]].
# Glutamate stimulates [[AMPA receptor|AMPA receptors]] and Ca2+-permeable [[NMDA receptor|NMDA receptors]], which open to allow more calcium into cells.
# Excess calcium entry overexcites cells and causes the generation of harmful chemicals like [[Free radical|free radicals]], [[reactive oxygen species]] and calcium-dependent [[Enzyme|enzymes]] such as [[calpain]], [[Endonuclease|endonucleases]], [[ATPase|ATPases]], and [[Phospholipase|phospholipases]] in a process called [[excitotoxicity]]. Calcium can also cause the release of more glutamate.
# As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.
# [[Mitochondrion|Mitochondria]] break down, releasing toxins and [[Apoptosis|apoptotic]] factors into the cell.
# The [[caspase]]-dependent [[apoptosis]] cascade is initiated, causing cells to "commit suicide."
# If the cell dies through [[necrosis]], it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby [[Neuron|neurons]], and glutamate can overexcite them.
# If and when the brain is reperfused, a number of factors lead to [[reperfusion injury]].
# An [[Inflammation|inflammatory]] response is mounted, and [[Phagocytosis|phagocytic]] cells engulf damaged but still viable tissue.
# Harmful chemicals damage the [[blood–brain barrier]].
# [[Cerebral edema]] (swelling of the brain) occurs due to leakage of large [[Molecule|molecules]] like [[albumins]] from blood vessels through the damaged [[blood brain barrier]]. These large molecules pull water into the brain tissue after them by [[osmosis]]. This "[[vasogenic edema]]" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases)."" ([[Ischemic cascade|Ischemic cascade - Wikipedia]])

The CRUCIAL elements of Ischemic Cascade are:

# this was only considered to be local, such as in the brain or a damaged area: conside this as as SYSTEM-WIDE reaction to system-wide hypoxia and endothelial cell damage as result of Influenza infection via Sialic Acid receptors, and also coronavirus infection by Covid19 via ACE2 receptors.
# NOTE: ACE2 receptor means: Angitension Converting Enzyme receptor with the purpose of converting Angiotensin II vasoconstrictor to Angiotensions 1-7 of which one is a vasodilator, and a trigger of NADPH antioxidant flourishing in the Krebs Cycle. 

__INDEX__
__NEWSECTIONLINK__

Ischemic Cascade

2024-05-11T05:26:15Z

Christopherd:corrected the syntax of a citation from wikipedia

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article is to theoreticall simplify the pathophysiology of CFS/ME symptoms by revisiting an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain, in response to a local condition of hypoxia.

Hypoxia appears to be the key issue in lack of exertion endurance in both skeletal muscle, and in the cognitive brain. Anecdotal reports have added that lowered emotional tolerance can precede or follow fatigue and "brain fog" in CFS/ME; that any one of the 3 areas of function can bring down either or both of the other two in a situation of exertion intolerance. This is further evidence that CFS/ME is not about a single pathogen, and is not about a single tissue. RATHER, as shown in the 2019 SARS-COV2 pandemic and sequelae, this condition can arise from various insults to the immune system but with the same result in the same systems.

Leading theory on the subject of Long-Covid sequelae indicates that blood vessel dysfunction, specifically endothelial cell dysfunction, is the key weak link in the otherwise healthy body system. But the blood vessels: capillary, vein, artery, become compromised by systemic infection and SYSTEM-WIDE deficiency. What is NOT much discussed is the possible cause of MODS, multiple organ dsyfunction syndrome which is resulting often in Long-Covid.

The reason for the scrutiny of this article on the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis/ SEID is that this Cascade of responses appears to have been delineated as a local condition in mainstream medicine, and most often as a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel damage and system-wide organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and weakened immune system function, may already have been defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae. If so, the definition of Ischemic Cascade may lead to the most direct intervention in ceasing the ME/CFS/SEID/Long-Covid obstacle to health.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease was established and adopted AFTER the previously mentioned disease monikers for the same condition.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies and furthermore overlooked in research as to their mitigation.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been redacted from the original mandatory 10 symptoms

POTS, or Postural Orthostatic Tachycardia Syndrome is the official name for such orthostatic intolerance.

What do ME/CFS/SEID/Long-Covid/POTS have in common?

INTOLERANCE.

And intolerance is a breach of homeostatic recovery.

NOTABLY: the key causative problem in MECFSSEIDLONGCOVID is:

a continued inflammation from a continued pathogen insult, long after the main infection has ceased.

Lastly, before describling the ISCHEMIC CASCADE stages, it is fitting to make a plausible reference

to latent viruses which can be reactivated in cells throughout the course of one's life,

putatatively because they evaded the patient's immune reaction and also eradication by

novel antibodies.

THE ISCHEMIC CASCADE of EVENTS in response to Hypoxia:

NOTE: You are free to attempt to read the PubMed explanation of Ischemic Cascade, at your own personal cost.

However, the following is quoted from Wikipedia [[Ischemic cascade|Ischemic cascade - Wikipedia]]<ref>{{Cite journal|title=Ischemic cascade|date=2024-02-09|url=https://en.wikipedia.org/w/index.php?title=Ischemic_cascade&oldid=1205244473|journal=Wikipedia|language=en}}</ref>

== "Mechanism ==
A [[Biochemical cascade|cascade]] is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events. In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:[''[[Wikipedia:Citation needed|citation needed]]'']

# Low blood supply decreases amount of oxygen that reaches tissues, leading to [[Hypoxia (medical)|hypoxia]]
# Deficiency of oxygen causes the neuron's normal process for making [[Adenosine triphosphate|ATP]] for energy to fail.
# The cell switches to [[Fermentation (biochemistry)|anaerobic metabolism]], producing [[lactic acid]].
# ATP-reliant [[Ion pump (biology)|ion transport pumps]] fail, causing the cell to become [[Action potential|depolarized]], allowing [[Ion|ions]], including [[calcium]] (Ca2+), to flow into the [[Cell (biology)|cell]].
# The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
# The presence of calcium triggers the release of the excitatory [[amino acid]] [[neurotransmitter]] [[glutamate]].
# Glutamate stimulates [[AMPA receptor|AMPA receptors]] and Ca2+-permeable [[NMDA receptor|NMDA receptors]], which open to allow more calcium into cells.
# Excess calcium entry overexcites cells and causes the generation of harmful chemicals like [[Free radical|free radicals]], [[reactive oxygen species]] and calcium-dependent [[Enzyme|enzymes]] such as [[calpain]], [[Endonuclease|endonucleases]], [[ATPase|ATPases]], and [[Phospholipase|phospholipases]] in a process called [[excitotoxicity]]. Calcium can also cause the release of more glutamate.
# As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.
# [[Mitochondrion|Mitochondria]] break down, releasing toxins and [[Apoptosis|apoptotic]] factors into the cell.
# The [[caspase]]-dependent [[apoptosis]] cascade is initiated, causing cells to "commit suicide."
# If the cell dies through [[necrosis]], it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby [[Neuron|neurons]], and glutamate can overexcite them.
# If and when the brain is reperfused, a number of factors lead to [[reperfusion injury]].
# An [[Inflammation|inflammatory]] response is mounted, and [[Phagocytosis|phagocytic]] cells engulf damaged but still viable tissue.
# Harmful chemicals damage the [[blood–brain barrier]].
# [[Cerebral edema]] (swelling of the brain) occurs due to leakage of large [[Molecule|molecules]] like [[albumins]] from blood vessels through the damaged [[blood brain barrier]]. These large molecules pull water into the brain tissue after them by [[osmosis]]. This "[[vasogenic edema]]" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases)."" ([[Ischemic cascade|Ischemic cascade - Wikipedia]])

The CRUCIAL elements of Ischemic Cascade are:

# this was only considered to be local, such as in the brain or a damaged area: conside this as as SYSTEM-WIDE reaction to system-wide hypoxia and endothelial cell damage as result of Influenza infection via Sialic Acid receptors, and also coronavirus infection by Covid19 via ACE2 receptors.
# NOTE: ACE2 receptor means: Angitension Converting Enzyme receptor with the purpose of converting Angiotensin II vasoconstrictor to Angiotensions 1-7 of which one is a vasodilator, and a trigger of NADPH antioxidant flourishing in the Krebs Cycle. 

__INDEX__
__NEWSECTIONLINK__

Ischemic Cascade

2024-05-11T05:23:35Z

Christopherd:added link to info source: Wikipedia Ischaemic Cascade

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article is to theoreticall simplify the pathophysiology of CFS/ME symptoms by revisiting an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain, in response to a local condition of hypoxia.

Hypoxia appears to be the key issue in lack of exertion endurance in both skeletal muscle, and in the cognitive brain. Anecdotal reports have added that lowered emotional tolerance can precede or follow fatigue and "brain fog" in CFS/ME; that any one of the 3 areas of function can bring down either or both of the other two in a situation of exertion intolerance. This is further evidence that CFS/ME is not about a single pathogen, and is not about a single tissue. RATHER, as shown in the 2019 SARS-COV2 pandemic and sequelae, this condition can arise from various insults to the immune system but with the same result in the same systems.

Leading theory on the subject of Long-Covid sequelae indicates that blood vessel dysfunction, specifically endothelial cell dysfunction, is the key weak link in the otherwise healthy body system. But the blood vessels: capillary, vein, artery, become compromised by systemic infection and SYSTEM-WIDE deficiency. What is NOT much discussed is the possible cause of MODS, multiple organ dsyfunction syndrome which is resulting often in Long-Covid.

The reason for the scrutiny of this article on the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis/ SEID is that this Cascade of responses appears to have been delineated as a local condition in mainstream medicine, and most often as a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel damage and system-wide organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and weakened immune system function, may already have been defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae. If so, the definition of Ischemic Cascade may lead to the most direct intervention in ceasing the ME/CFS/SEID/Long-Covid obstacle to health.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease was established and adopted AFTER the previously mentioned disease monikers for the same condition.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies and furthermore overlooked in research as to their mitigation.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been redacted from the original mandatory 10 symptoms

POTS, or Postural Orthostatic Tachycardia Syndrome is the official name for such orthostatic intolerance.

What do ME/CFS/SEID/Long-Covid/POTS have in common?

INTOLERANCE.

And intolerance is a breach of homeostatic recovery.

NOTABLY: the key causative problem in MECFSSEIDLONGCOVID is:

a continued inflammation from a continued pathogen insult, long after the main infection has ceased.

Lastly, before describling the ISCHEMIC CASCADE stages, it is fitting to make a plausible reference

to latent viruses which can be reactivated in cells throughout the course of one's life,

putatatively because they evaded the patient's immune reaction and also eradication by

novel antibodies.

THE ISCHEMIC CASCADE of EVENTS in response to Hypoxia:

NOTE: You are free to attempt to read the PubMed explanation of Ischemic Cascade, at your own personal cost.

However, the following is quoted from Wikipedia [[Ischemic cascade|Ischemic cascade - Wikipedia]]

== "Mechanism ==
A [[Biochemical cascade|cascade]] is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events. In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:[''[[Wikipedia:Citation needed|citation needed]]'']

# Low blood supply decreases amount of oxygen that reaches tissues, leading to [[Hypoxia (medical)|hypoxia]]
# Deficiency of oxygen causes the neuron's normal process for making [[Adenosine triphosphate|ATP]] for energy to fail.
# The cell switches to [[Fermentation (biochemistry)|anaerobic metabolism]], producing [[lactic acid]].
# ATP-reliant [[Ion pump (biology)|ion transport pumps]] fail, causing the cell to become [[Action potential|depolarized]], allowing [[Ion|ions]], including [[calcium]] (Ca2+), to flow into the [[Cell (biology)|cell]].
# The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
# The presence of calcium triggers the release of the excitatory [[amino acid]] [[neurotransmitter]] [[glutamate]].
# Glutamate stimulates [[AMPA receptor|AMPA receptors]] and Ca2+-permeable [[NMDA receptor|NMDA receptors]], which open to allow more calcium into cells.
# Excess calcium entry overexcites cells and causes the generation of harmful chemicals like [[Free radical|free radicals]], [[reactive oxygen species]] and calcium-dependent [[Enzyme|enzymes]] such as [[calpain]], [[Endonuclease|endonucleases]], [[ATPase|ATPases]], and [[Phospholipase|phospholipases]] in a process called [[excitotoxicity]]. Calcium can also cause the release of more glutamate.
# As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.
# [[Mitochondrion|Mitochondria]] break down, releasing toxins and [[Apoptosis|apoptotic]] factors into the cell.
# The [[caspase]]-dependent [[apoptosis]] cascade is initiated, causing cells to "commit suicide."
# If the cell dies through [[necrosis]], it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby [[Neuron|neurons]], and glutamate can overexcite them.
# If and when the brain is reperfused, a number of factors lead to [[reperfusion injury]].
# An [[Inflammation|inflammatory]] response is mounted, and [[Phagocytosis|phagocytic]] cells engulf damaged but still viable tissue.
# Harmful chemicals damage the [[blood–brain barrier]].
# [[Cerebral edema]] (swelling of the brain) occurs due to leakage of large [[Molecule|molecules]] like [[albumins]] from blood vessels through the damaged [[blood brain barrier]]. These large molecules pull water into the brain tissue after them by [[osmosis]]. This "[[vasogenic edema]]" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases)."" ([[Ischemic cascade|Ischemic cascade - Wikipedia]])

The CRUCIAL elements of Ischemic Cascade are:

# this was only considered to be local, such as in the brain or a damaged area: conside this as as SYSTEM-WIDE reaction to system-wide hypoxia and endothelial cell damage as result of Influenza infection via Sialic Acid receptors, and also coronavirus infection by Covid19 via ACE2 receptors.
# NOTE: ACE2 receptor means: Angitension Converting Enzyme receptor with the purpose of converting Angiotensin II vasoconstrictor to Angiotensions 1-7 of which one is a vasodilator, and a trigger of NADPH antioxidant flourishing in the Krebs Cycle. 

__INDEX__
__NEWSECTIONLINK__

User talk:Christopherd

2024-05-11T05:17:41Z

Christopherd:/* Ischemic cascade article -- JaimeS (talk) 13:38, May 9, 2024 (UTC) */

{{Template:Welcome|realName=Chris D|name=Christopherd}}

-- [[User:New user message|New user message]] ([[User talk:New user message|talk]]) 01:53, May 9, 2024 (UTC)

== Ischemic cascade article -- [[User:JaimeS|JaimeS]] ([[User talk:JaimeS|talk]]) 13:38, May 9, 2024 (UTC) ==

Hello, Christopher D!

Please note that every piece of info on MEpedia needs to be cited. Please revisit the Science Guidelines on MEpedia and cite everything you state by using the "Cite" button at the top of the screen.

===Re: Ischemic cascade article -- [[User:Christopherd|Christopherd]] ([[User talk:Christopherd|talk]]) 05:17, May 11, 2024 (UTC)===

: I shall, but I need to write it first before I know what to cite

Ischemic Cascade

2024-05-09T04:04:15Z

Christopherd:large amounts

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article is to potentially simplify the pathophysiology of CFS/ME symptoms by revisiting an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain, in response to a local condition of hypoxia.

Hypoxia appears to be the key issue in lack of exertion endurance in both skeletal muscle, and in the cognitive brain. Anecdotal reports have added that lowered emotional tolerance can precede or follow fatigue and "brain fog" in CFS/ME. That any one of the 3 areas of function can bring down either or both of the other two in a situation of exertion intolerance. This is further evidence that CFS/ME is not about a single pathogen, and is not about a single tissue. RATHER, as shown in the 2019 SARS-COV2 pandemic and sequelae, this condition can arise from various insults to the immune system but with the same result.

Leading theory on this subject indicates that blood vessel dysfunction, specifically endothelial cell dysfunction, is the key weak link in the otherwise healthy body system. But the blood vessels: capillary, vein, artery, become compromised by systemic infection and SYSTEM-WIDE deficiency.

The reason for this scrutiny of the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome, Myalgic Encephalomyelitis and SEID is that this Cascade of responses appears to have been delineated as a local condition, and most often a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel damage and system-wide organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and weakened immune system function, may already have been defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae. If so, the definition of Ischemic Cascade may lead to the most direct intervention in ceasing the ME/CFS/SEID/Long-Covid obstacle to health.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease was established and adopted AFTER the previously mentioned disease monikers for the same condition.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies and furthermore overlooked in research as to their mitigation.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been redacted from the original mandatory 10 symptoms

POTS, or Postural Orthostatic Tachycardia Syndrome is the official name for such orthostatic intolerance.

What do ME/CFS/SEID/Long-Covid/POTS have in common?

INTOLERANCE.

And intolerance is a breach of homeostatic recovery.

NOTABLY: the key causative problem in MECFSSEIDLONGCOVID is:

a continued inflammation from a continued pathogen insult, long after the main infection has ceased.

Lastly, before describling the ISCHEMIC CASCADE stages, it is fitting to make a plausible reference

to latent viruses which can be reactivated in cells throughout the course of one's life,

putatatively because they evaded the patient's immune reaction and also eradication by

novel antibodies.

THE ISCHEMIC CASCADE of EVENTS in response to Hypoxia:

NOTE: You are free to attempt to read the PubMed explanation of Ischemic Cascade, at your own personal cost.

However, the following is quoted from Wikipedia ([[Ischemic cascade|Ischemic cascade - Wikipedia]])

== "Mechanism ==
A [[Biochemical cascade|cascade]] is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since the events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events. In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:[''[[Wikipedia:Citation needed|citation needed]]'']

# Low blood supply decreases amount of oxygen that reaches tissues, leading to [[Hypoxia (medical)|hypoxia]]
# Deficiency of oxygen causes the neuron's normal process for making [[Adenosine triphosphate|ATP]] for energy to fail.
# The cell switches to [[Fermentation (biochemistry)|anaerobic metabolism]], producing [[lactic acid]].
# ATP-reliant [[Ion pump (biology)|ion transport pumps]] fail, causing the cell to become [[Action potential|depolarized]], allowing [[Ion|ions]], including [[calcium]] (Ca2+), to flow into the [[Cell (biology)|cell]].
# The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
# The presence of calcium triggers the release of the excitatory [[amino acid]] [[neurotransmitter]] [[glutamate]].
# Glutamate stimulates [[AMPA receptor|AMPA receptors]] and Ca2+-permeable [[NMDA receptor|NMDA receptors]], which open to allow more calcium into cells.
# Excess calcium entry overexcites cells and causes the generation of harmful chemicals like [[Free radical|free radicals]], [[reactive oxygen species]] and calcium-dependent [[Enzyme|enzymes]] such as [[calpain]], [[Endonuclease|endonucleases]], [[ATPase|ATPases]], and [[Phospholipase|phospholipases]] in a process called [[excitotoxicity]]. Calcium can also cause the release of more glutamate.
# As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.
# [[Mitochondrion|Mitochondria]] break down, releasing toxins and [[Apoptosis|apoptotic]] factors into the cell.
# The [[caspase]]-dependent [[apoptosis]] cascade is initiated, causing cells to "commit suicide."
# If the cell dies through [[necrosis]], it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby [[Neuron|neurons]], and glutamate can overexcite them.
# If and when the brain is reperfused, a number of factors lead to [[reperfusion injury]].
# An [[Inflammation|inflammatory]] response is mounted, and [[Phagocytosis|phagocytic]] cells engulf damaged but still viable tissue.
# Harmful chemicals damage the [[blood–brain barrier]].
# [[Cerebral edema]] (swelling of the brain) occurs due to leakage of large [[Molecule|molecules]] like [[albumins]] from blood vessels through the damaged [[blood brain barrier]]. These large molecules pull water into the brain tissue after them by [[osmosis]]. This "[[vasogenic edema]]" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases).""

The CRUCIAL elements of Ischemic Cascade are:

# this was only considered to be local, such as in the brain or a damaged area: conside this as as SYSTEM-WIDE reaction to system-wide hypoxia and endothelial cell damage as result of Influenza infection via Sialic Acid receptors, and also coronavirus infection by Covid19 via ACE2 receptors.
# NOTE: ACE2 receptor means: Angitension Converting Enzyme receptor with the purpose of converting Angiotensin II vasoconstrictor to Angiotensions 1-7 of which one is a vasodilator, and a trigger of NADPH antioxidant flourishing in the Krebs Cycle. 

__INDEX__
__NEWSECTIONLINK__

Ischemic Cascade

2024-05-09T03:58:18Z

Christopherd:

Ischemic Cascade

2024-05-09T03:40:04Z

Christopherd:major new section title

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article is to potentially simplify the pathophysiology of CFS/ME symtpoms by revisiting an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain, in response to a local condition of hypoxia.

The reason for this scrutiny of the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome, Myalgic Encephalomyelitis and SEID is that this Cascade of responses appears to have been delineated as a local condition, and most often a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel damage and system-wide organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and weakened immune system function, may already have been defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae. If so, the definition of Ischemic Cascade may lead to the most direct intervention in ceasing the ME/CFS/SEID/Long-Covid obstacle to health.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease was established and adopted AFTER the previously mentioned disease monikers for the same condition.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies and furthermore overlooked in research as to their mitigation.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been redacted from the original mandatory 10 symptoms

POTS, or Postural Orthostatic Tachycardia Syndrome is the official name for such orthostatic intolerance.

What do ME/CFS/SEID/Long-Covid/POTS have in common?

INTOLERANCE.

And intolerance is a breach of homeostatic recovery.

NOTABLY: the key causative problem in MECFSSEIDLONGCOVID is:

a continued inflammation from a continued pathogen insult, long after the main infection has ceased.

Lastly, before describling the ISCHEMIC CASCADE stages, it is fitting to make a plausible reference

to latent viruses which can be reactivated in cells throughout the course of one's life,

putatatively because they evaded the patient's immune reaction and also eradication by

novel antibodies.

THE ISCHEMIC CASCADE of EVENTS in response to Hypoxia:

__INDEX__
__NEWSECTIONLINK__

Ischemic Cascade

2024-05-09T03:38:37Z

Christopherd:addition of info on latent viruses

Ischemic Cascade

2024-05-09T03:31:00Z

Christopherd:new info

Ischemic Cascade

2024-05-09T03:22:33Z

Christopherd:some grammar

{{DISPLAYTITLE:Ischemic Cascade as May Explain ME/CFS}}

The intention of the following article is to potentially simplify the pathophysiology of CFS/ME symtpoms by revisiting an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain, in response to a local condition of hypoxia.

The reason for this scrutiny of the condition "Ischemic Cascade" in context of Chronic Fatigue Syndrome, Myalgic Encephalomyelitis and SEID is that this Cascade of responses appears to have been delineated as a local condition, and most often a brain condition... but a system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may well aptly explain the syndrome.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel and organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and low immune system function, could be already defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease has been established and adopted AFTER the previously mentioned disease monikers.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been reduced from the original mandatory 10 symptoms

__INDEX__
__NEWSECTIONLINK__

Ischemic Cascade

2024-05-09T02:58:52Z

Christopherd:added a paragraph on the criteria for diagnosis

The intention of the following article is to harken back to an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain, in response to a local condition of hypoxia. The reason for this scrutiny of the condition "Ischemic Cascade" in context of Myalgic Encephalomyelitis and SEID is that this Cascade of responses appears to have been delineated as a local condition, and most often a brain condition... but system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may aptly explain it.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel and organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and low immune system function, could be already defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease has been established and adopted AFTER the previously mentioned disease monikers.

This article seeks to bring to light an already-medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID studies.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months. It indicates a chronic state of feelings of physical fatigue, coupled with bouts of Post Exertional Malaise and also Unrefreshing sleep, as the 3 indisputable symptoms. This leaves two other symptoms of which one or the other must be present in order for the condition to qualify or be diagnosed as CFS/ME/SEID:

Either cognitive impairment

or

Orthostatic intolerance.

or both.

These 5 current criteria have been reduced from the original mandatory 10 symptoms

Ischemic Cascade

2024-05-09T02:49:17Z

Christopherd:a few grammar changes

The intention of the following article is to harken back to an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in one region of the body, most often the brain, in response to a local condition of hypoxia. The reason for this scrutiny of the condition "Ischemic Cascade" in context of Myalgic Encephalomyelitis and SEID is that this Cascade of responses appears to have been delineated as a local condition, and most often a brain condition... but system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID and may aptly explain it.

Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel and organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even effected by patient-specific bacterial infections and low immune system function, could be already defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae.

The following standards are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease has been established and adopted AFTER the previously mentioned disease monikers.

This article seeks to bring to light a medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID medically approved terminologies.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months.

Ischemic Cascade

2024-05-09T02:45:49Z

Christopherd:amplified the introduction and purpose

The intention of the following article is to harken back to an already-established medical condition called Ischemic Cascade which is a 16 stage cascade of body reactions aimed at restoring homeostasis in a region of the body, most often the brain, in response to a local condition of hypoxia. The reason for this scrutiny of the condition "Ischemic Cascade" in context of Myalgic Encephalomyelitis and SEID is that this Cascade of responses appears to have been delineated as a local condition, and most often a brain condition... but system-wide predominance of this condition has not been widely considered as an explanation or definition of CFS/ME/SEID. Since SEID is a system-wide intolerance to exertion, and since the "IC" phases closely resemble its symptoms, it appears prudent to consider that system-wide blood vessel and organ damage effected by (not a-ffected by) Covid19 or previous Influenza pandemics, and even patient-specific bacterial infections and exhaustion, could be already defined in the definition of Ischemic Cascade, and could quite potentially explain the following definitive symptoms of CFS/ME/SEID, and lately, Long-Covid sequelae.

The following are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease has been established and ACCEPTED after the previously mentioned disease monikers.

This article seeks to bring to light a medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID medically approved terminologies.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months.

Ischemic Cascade

2024-05-09T02:30:54Z

Christopherd:Defined CFS/ME/SEID in tandem

The following are clear to the author: the Canadian Consensus criteria and the Fukuda criteria for diagnosing an ailment as Chronic Fatigue Syndrome.

The appellation SEID or Systemic Exertion Intolerance Disease has been established and ACCEPTED after the previously mentioned disease monikers.

This article seeks to bring to light a medically established phenomenon which seems to have been overlooked in the CFS/ME/SEID medically approved terminologies.

Chronic Fatigue Syndrome as a medical appellation seems to indicate the obvious, that the symptoms have lasted past the 3-month appellation time limit for a disease being considered to be in the ACUTE stage of up to 3 months.