Spreading Depo; Flashcards
How does spreading depol occur
NaK ATPase dysfunctioning, Water follows sodium and calcium ions entering the intracellular space (cytotoxic edema) because these outnumber the potassium ions leaving the cells
What is a Direct Current potential
A potential observed in extracellular recording during spreading depolarization as a large negative change of the slow electrical field potential
Trigger for spreading depol/brain tsunami
pathological conditions such as intoxication with chemicals (e.g. potassium), pharmacological inhibition of the sodium-potassium pump (Na/K-ATPase) or the respiratory chain, or during hypoxia, hypoglycemia, brain trauma or stroke; haemorrhage, migraine aura
Measuring for spreading DEPRESSION of activity
SDepol induces a silencing or suppression of spontaneous brain electrical activity, observed in the alternating current (AC) range of electrocorticographic (ECoG) recordings as amplitude reductions that run between adjacent electrodes.
Where does SD occur?
Only in grey matter
When will SDepression NOT occur?
In “isoelectric”tissue, where the spontaneous activity has already been depressed e.g. by previous spreading depolarizations, does not lead to depression
Spreading depol can occur.
After spreading depol,
spreading depression occur as a consequences
What’s the speed of spreading depol
they last for at least 30 seconds and propagate in the tissue at a rate of about 3 mm/min
What is Neurovascular coupling
process of increase in neuronal activity requires vasodilation, and accordingly an increase in CerebralBloodFlow to meet the increased energy demand
cf hyperremia
What is the normal neurovascular response to spreading depolarization
the release of glutamate and vasoeffectors (likenitric oxide (NO)and arachidonic acid metabolites), ion flux directions, and increase in metabolism and energy demand
How does CBF change in SDepol
Under physiological conditions, CBF increases in response to spreading depolarization by more than 100%. This CBF increase typically propagates together with the depolarization wave in the tissue. It is therefore termedspreading hyperemia. Spreading hyperemia 充血seems to serve several purposes: increased delivery of energy substrates (glucose, oxygen) to the tissue, and increased clearance of metabolites from the extracellular space. It outlasts spreading depolarization and only ends after about two minutes. Following spreading hyperemia, CBF shows a mild decrease for up to two hours. This type of mild CBF reduction in response to spreading depolarization is calledspreading oligemia血液減少症.
Spreading Hyperemia
Part of neurovascular coupling lead by Sdepol where CBF increases to increased delivery of energy substrates (glucose, oxygen) to the tissue, and increased clearance of metabolites from the extracellular space. Last for about 2 min.
spreading oligemia
Reduction of CBF after SHyperemia (increase of CBF after Sdepol)
How is prolonged hypoperfusion caused by Sdepol?
when there is local dysfunction of the microvasculature, and instead of vasodilation, microarterial spasm is coupled to the neuronal depolarization
This leads to prolonged depol phase ( observed as a prolonged negative DC shift)
Important as it alters harmless Sdepol to cortical necrosis 壊死
spreading ischemia
hypoperfusion as a consequence of the inverse CBF response to spreading depolarization, while spreading oligemia is harmless
Can be triggered by decrease of cortical NO availability combined with an increase in baseline extracellular potassium
What is ischemic penumbra
“intermediate” characteristics of spreading depol between normal and severely ischemic brain
Region of constrained blood supply and disturbed protein synthesis where energy metabolism is still preserved; mostly rescuable
Neurons are not terminally depolarised but CBF is low (Depression cannot occur)
What is lead by cerebral ischemia
Cerebral ischemia -> after 2-5min: “anoxic” spreading depol ( -> if lasted for long enough, passed the commitment point, neurons die)
If the tissue is reperfused right, neurons survive
How does it look like in the Ecog?
Healthy: curve like a fancy hat. Start, opposite of U, end at the same as start level
Penumbra: Not a symmetrical oppU but takes longer time to repol
Ischemia: reaches the top of oppU and keep on increasing
How does Penumbra occur?
Starting from the focal ischemic core, it spreads against the gradients of oxygen, glucose, and perfusion into the adequately supplied surrounding tissue, changing its features in response to the local conditions of the tissue during the course of its propagation. By the time it has reached the surrounding non-ischemic tissue, the initially anoxic spreading depolarization will have become a short-lasting non-ischemic spreading depolarization. In other words, the full continuum of spreading depolarization is observed in this single initial wave, as well as in subsequent spontaneous depolarization waves. It is also important to realize that the pharmacological sensitivity of spreading depolarizations to spreading depolarization-inhibiting drugs increases along the continuum.
What does duration of the negative DC shift of spreading depolarization indicate?
duration of the depolarization and near-complete breakdown of the ion homeostasis
the negative DC shift is a powerful indicator of both tissue energy status and the risk of injury at the recording site.
What does repol require?
Repolarization requires activation of the energy-dependent Na/K-ATPase. Short-lasting DC shifts therefore indicate sufficient ATP supplies for repolarization at the recording site
How to study SDepol in ischemic penumbra?
model of middle cerebral artery occlusion in animals
shown that the cumulative duration of spreading depolarizations correlated with infarct size and growth
Animal model helped to understand deleterious effect of Sdepol
endothelin-1 (ET-1) model in rats
-Area where ET1 was applied,
1) half decreased blood and caused Sdepol -> necrosis
2) half did not lead to Sdepol unless chemically triggered
Result:
depolarization waves initiated the cellular damage in the low-flow region, independently of whether the depolarization wave started in the healthy surrounding cortex or in the low-flow region
Why is migraine aura and stroke similar yet only latter leads to neuronal injury?
The spreading depolarization process – depending on its duration – thus initiates the countdown to neuronal death, whereas the depression pattern determines the clinical symptoms
ischemia causes non-spreading depression of activity, due to the harmless spreading Dpol. (Harmless become harmful as depression cannot occur to propagate). This leads to complete electrical failure and a sudden onset of symptoms such as hemiparesis or aphasia
What is traumatic penumbra?
Caused by Traumatic Brain Injury; spreading depol can be measured in 56% of patients with severe TBI.
one significant difference between the ischemic and the traumatic penumbra: penumbral tissue in ischemia shows a pathologically elevated oxygen extraction fraction (OEF), whereas in the traumatic penumbra OEF is low
Spreading depolarization in aneurysmal SAH (aSAH)
- second most common type of hemorrhagic stroke
- results from the rupture of a basal cerebral artery aneurysm
- Among survivors, only 60% are able to resume their previous lifestyles.
- Delayed cerebral ischemia (DCI) is the most prominent in-hospital complication after aSAH and it is presumably caused by the breakdown of erythrocyte products in the subarachnoid space
- Ecog: clusters of recurrent spreading depolarizations with prolonged depression of the spontaneous activity indicate the occurrence of DC
Spreading depolarization in ischemic stroke
- In addition to DCI, malignant hemispheric stroke (MHS) is the other type of ischemic stroke in which spreading depolarizations can be monitored in patients
- It occurs in around 10% of patients with middle cerebral artery infarcts
- These patients have massive infarctions that require a decompressive hemicraniectomy to avoid life-threatening brain edema (and increased intracranial pressure)
- Spreading depolarizations occur in practically 100% of patients with MHS
Which parts of the neuron show the most impressive changes when a cytotoxic edema develops?
spines on the dendrites diminishes (swells)
aka dendritic beading
What happens during an action potential (do the ionic concentrations of the bulk solutions change or does it only represent a change in membrane potential with neglegible exchange of ions across the membrane)?
Only represent a change in Vm with neligible exchange, otherwise it will swell all the time
How much energy costs an action potential in relation to the energy contained in the ion concentration gradients across the membrane?
Not so much, when it is a lot, it leads to epileptic seizure, spreading depol or even death
For electrocorticographic seizure activity, what is more reliable?
DC not 0.5 Hz high-pass filter
Difference between causing short depression vs long depression
short: spreading hyperaemia充血, short SPC
long: spreading ischemia局所貧血, long SPC
Spreading oligemia vs spreading ischemia
Both is talking about reduction in blood flow
Oli is “healthy” response to increase CBF after spreading hyperemia
Ischemia is “unhealthy” response to inverse neurovascular coupling
What perpetuate (elongate) the duration of spreading ischemia?
due to disturbed microvascular reactivity
caused by decrease in cortical NO availability and increased K in the extracellular
Inverse neurovascular coupling
This occurs when there is local dysfunction of the microvasculature, and instead of vasodilation, microarterial spasm痙攣 (causing constrtiction) is coupled to the neuronal depolarization
This leads to prolonged depol and DC.
Risk of Inverse neurovascular coupling
Neuron needs more blood while the delivery is lowered, changing the none harmful spreading Dpol to harmful.
Worst case leading to cortical necrosis
What is determined by the duration of spreading depolarization? What is determined by the type of depression?
The duration of the spreading depolarization determines whether or not it will harm the tissue whereas the depression pattern determines the nature of the clinical symptoms. In well-supplied tissue, spreading depression causes a spreading focal neurological deficit. In energy depleted tissue, non-spreading depression of activity causes an apoplectiform focal deficit in various neurological functions.
Is non-spreading depression induced by spreading depolarization?
No, non-spreading depression of activity precedes spreading depolarization and is triggered by other processes such as ischemia. Importantly, neurons are hyperpolarized during non-spreading depression of activity
Is spreading depression induced by spreading depolarization
Yes. Spreading depression results from a depolarization block of activity.
Which of the folloing answer/s is/are true?
During spreading depolarization, water enters cells following
Potassium influx
Sodium influx
Potassium outflux
Calcium influx
Calcium outflux
Sodium influx
Calcium influx
Potassium outflux
Spreading depolarizations are limited to
gray matter
The restoration of the ion gradients following spreading depolarization is mainly driven by the Na-/K-ATPase. It is an energy dependent mechanism that subsequently leads to an increase in _____
The restoration of the ion gradients following spreading depolarization leads to an increase in regional cerebral blood flow. (3Na out, 2K in)
Which enzyme is the single greatest energy consumer in mammalian cells, and especially in excitable cells?
Under resting conditions, the sodium-potassium pump (Na/K-ATPase) accounts for roughly 50 % of the brain’s energy consumption. This fraction increases even further following the massive ion translocation during spreading depolarization
What is the role of ATP during spreading depolarization?
Energy in the form of ATP is spent to maintain the steep ionic gradients across the neuronal cell membranes. This ensures the cell’s excitability (e.g. generation of action potentials) and powers secondary active transmembrane transport.
Spreading depolarizations have been detected in abundance in patients with (pick false) aneurysmal subarachnoid hemorrhage epilepsy traumatic brain injury malignant hemispheric stroke
epilepsy
During spreading ischemia… (pick false)
- spreading depolarizations lead to an initial tissue hypoperfusion
- short-lasting spreading depolarizations can turn into harmful intermediate or terminal spreading depolarizations
- spreading ischemia and spreading oligemia are essentially synonyms
- the prolonged neuronal depolarization leads to a prolongation of the negative DC-shift
- spreading ischemia and spreading oligemia are essentially synonyms
What is the difference between spreading ischemia and spreading oligemia?
Spreading ischemia is a severe vasoconstriction triggered by spreading depolarization. Spreading ischemia creates a perfusion deficit that prevents neuronal repolarization and prolongs the release of vasoconstrictors. In electrophysiological recordings, spreading ischemia presents with a prolonged negative DC-shift of spreading depolarization.
Spreading oligemia is a mild long-lasting hypoperfusion that variably follows the pronounced hyperemia during the normal neurovascular response to spreading depolarization.
Spreading depolarizations occur in approximately
_____% of patients with malignant hemispheric stroke,
_____% of patients with aneurysmal subarachnoid hemorrhage, and
_____% of patients with severe traumatic brain injury
100, 70-80, 56
Cytotoxic Edema
- is an inevitable consequence of spreading depolarization due to ionic breakdown and water movement into the cells
- happens in most occasions as consequence of water movement into the cells
- only happens when there is no recovery following spreading depolarization
- is an irreversible event following spreading depolarization
is an inevitable consequence of spreading depolarization due to ionic breakdown and water movement into the cells
