|
Description:
|
According to the American Stroke Association , about 700 ,000 people suffer a new or recurrent stroke each year in the United States . Of these people , approximately 163 ,000 die , making stroke the third leading cause of death in the U .S . , only behind heart disease and cancer . Depending on the area of the brain affected by the stroke , functions such as motor activity , speech , behavior , and /or memory can be hampered . The hippocampus is a bilateral structure that is highly susceptible to hypoxic and /or ischemic insult .
One of the early responses to ischemia is the transient and reversible inhibition of synaptic activity mediated by endogenous adenosine acting on neuronal A1 receptors . Increase in adenosine during ischemia is thought to play a key prosurvival role by attenuating excitotoxic damage through inhibiting glutamate release and activating Akt .
Akt is activated by PI3K -dependent and PI3K -independent mechanisms . Akt , also known as PKB , has been shown to be both necessary and sufficient to promote cell survival by growth factors in vitro . Akt directly phosphorylates multiple proteins resulting in the inhibition of apoptotic and /or necrotic cell death . Bcl -2 and Bcl -xL are two proteins that are disinhibited by the direct Akt phosphorylation of Bad . These two proteins function to maintain mitochondrial integrity during ischemia , thus inhibiting the release of cytochrome c which is a strong inducer of the apoptotic pathway .
This thesis explores the activation mediated by PI3K and the significance of this activation in neuronal survival mechanisms . |