ischemia reperfusion Flashcards
What is the nutrition the brain uses in suckling new borns?
Ketone bodies
-milk has a high fat content
Glutamate and GABA are what type of molecules for neurons?
Glutamate - excitatory
GABA - inhibitory
PET imaging shows glucose and o2 metabolism in the brain by way of assayin the hexokinase reaction through what analogs of glucose?
2-deoxy glucose
2-fluoro-deoxy glucose
Magnetic resonance spectroscopy uses what substance to measure metabolism in the brain?
Radioactive substances: 3H, 14C, 11C or stable isotope 13C
Focal cerebral ischemia
Local disruption of blood flow to a part of the brain, due to occlusion of an artery by embolus.
Umbra: injury area with no oxygen/nutrients
Penumbra - area surrounding the umbra that is also at risk for cell death.
Perfusion in penumbra can be restored by thrombolytic agents
The area of injury is usually smaller than the distribution of the occluded artery because the brain compensates by collateral circulation.
Global cerebral ischemia
Transient impairment of blood flow to whole brain, happens during cardiac arrest.
Most vulnerable: hippocampus pyramidal cell of CA 1 region and purkinje cell and striata neurons
Least vulnerable or most resistant: CA3 in hippocampus and granule cells in dentate gyrus
What is the general cascade of biochemical events following ischemia?
Blood flow blocked Reduction or absence of O2 and glucose Metabolism impaired ATP levels reduced Ion pump dysfunction -cant run without ATP Disruption of ion gradient -Na+ and Ca++ most importantly Membrane depolarization -from the Na+ Opening of voltage gated channels -depolarization Signalling cascade -Ca++ Influx of Ca++ into cell. -wreck intracellular havoc NT released Cell death
What is the target receptor that induces cell death? How is it blocked?
DAPK1 binding the receptorNMDA causes neuronal cell death, blocking this with the drug NR2B-CT saves the cell from death during stroke.
What is excitotoxicity? How does it cause cause injury to the brain?
Overactivation of NMDA and AMPA/kainate causes ecitotoxiticity. More specifically by the loss of ion grandients.
Leads to a build up of glutamate and over activation of the glutamate receptors ^^^^. These are calcium channel, when activated causes a cellular uptake of Ca++.
elevated [Ca++]intracellular causes release of NT.
It’s the intracellular Ca++ that really does the damage: calpain degrades cytoskelton, damages mitochondria, generates reactive oxygen species, damages membrane stability and causes the inactivation of synthetic enzymes.
Why is it detrimental to reperfuse the ischemic brain tissue too quickly following a stroke?
It’s damaging to the blood brain barrier, causes the permeability to increase and capillary endothelial cell death. The death recruients leukocytes and plugs blood vessels. -> hemorrhage. And Edema. (From cytokines and inflammation)
