Access Type

Open Access Thesis

Date of Award

January 2012

Degree Type


Degree Name




First Advisor

Donald J. DeGracia


Brain ischemia and reperfusion that occurs after stroke and cardiac arrest, causes translation arrest (TA) in neurons which is irreversible in neurons that will undergo delayed neuronal death. TA is linked to mRNA granules, which are involved in ischemia-induced stress genes translation. Ischemic preconditioning (IPC) is the most protective response known that protects neurons from a lethal ischemic insult. In this thesis I studied the effects of (1) sublethal durations of ischemia, (2) IPC and (3) cycloheximide (CHX) on the formation of mRNA granules at 1 hour of reperfusion and the colocalization of HuR in the mRNA granules. All durations tested, from 2 to 8 min ischemia caused formation of mRNA granules, and HuR colocalized in the mRNA granules at lower ischemia durations in CA1 neurons. However, IPC appeared to attenuate the formation of mRNA granules at 1 hour reperfusion and did not enhance HuR colocalization. CHX inhibited mRNA granules at 1 hour reperfusion, but had no effect in animals subjected to prior IPC. These results show that sublethal durations of ischemia cause CA1 neurons to behave similarly to CA3 neurons. However, the mRNA granule response appears to be less important after a 10 min ischemia in preconditioned animals. These results show that the 10 min ischemia period is perceived differently by the preconditioned CA1 neuron compared to a non-preconditioned neuron. Moreover, these results shed important light on the post-ischemic neuronal response, and will help in the effort to develop effective therapies to protect against stroke and cardiac arrest brain damage.

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