Term
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Definition
•Clinically defined syndrome of quickly developing symptoms of focal loss of cerebral function with no apparent cause other than that of vascular origin (loss of function can sometimes be global, i.e. coma).
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Term
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Definition
•Ischemic- Blockage of arterial vessel due to thrombus and/or embolic event.
–Atherosclerosis of vessels is typical culprit
•Hemorrhagic- Physical rupture of arterial vessel resulting in bleeding.
–Hypertension and/or aneurysm is typically responsible.
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Term
Paradigm for Neuronal Preservation |
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Definition
-The critical factor for survival of neuronal tissue during a stroke is the balance between energy demand and energy supply.
This brings up two important points:
- improvement of blood flow
- reduction of brain energy demand
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Term
Loss of Blood-Brain Barrier
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Definition
•BBB typically restricts solute and cellular flow across vessels.
•Stroke results in loss of tight junction integrity and protein expression (occludin, claudin, ZO-1).
•Loss of tight junctions are permissive for increased permeability and leukocyte efflux out of the vasculature.
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Term
Mechanisms of BBB Breakdown |
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Definition
•Excitotoxcity
–Glutamate-receptor signaling in endothelial and glial cells and astrocytes.
•Loss of glucose
–Altered ATP production and ion imbalance
•Inflammatory injury
–Cellular
•Leukocytes
•Platelets
–Chemical (ROS/RNS)
–Cytokine/Chemokine
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Term
Tissue Ischemia
Dramatically Alters ......
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Definition
-Mitochondrial Function and Oxidative
Phosphorylation
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Term
So, what do mitochondria do?
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Definition
-• Make ATP
• Ca2+ signaling (buffering)
• Re-generate NADH for glycolysis
• Urea Cycle
• Biosynthesis of amino acids, heme, steroid hormones
• “Gatekeepers” for apoptotic signaling (cytochrome c)
• Make heat (esp. brown adipose tissue)
• Generate free radicals for cell-signaling
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Term
Complex II is a K+ ATP Channel
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Definition
-• Opening of channel underlies the phenomenon of “ischemic preconditioning” (IPC), in which a short period of ischemia can protect the heart from a longer sustained ischemia later on.
• Many drugs that open the channel (e.g. diazoxide) are also complex II inhibitors
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Term
Mitochondria make Reactive Oxygen Species
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Definition
• ROS = Reactive oxygen species (a.k.a. free radicals)…
• Complex I à ROS from the FMN site, facing in.
• Complex III à ROS from semiquinone, on both sides of the membrane.
• Some debate as to whether O2·- or HO2· is formed.
• O2·- cannot leave mitochondrial matrix. H2O2 can freely diffuse out.
• Role in aging process (Harman theory) vs. role in cell signaling?
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