Graduation Year

2010

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Molecular Pharmacology and Physiology

Major Professor

Enrico Camporesi, M.D.

Co-Major Professor

Dave Morgan, Ph.D.

Committee Member

Marcia N. Gordon, Ph.D.

Committee Member

Hans Schweiger, M.D.

Committee Member

Nagwa Dajani, Ph.D.

Keywords

hypotension, caspase, stroke, hypoxia, anesthesia

Abstract

Neuroprotection with anesthetics has been studied for many decades; important advances in this field have modified the way Anesthesiologists treat patients in the operating room. Animal models have played an important role in the study of ischemia in the operating room. Recent studies have demonstrated that the effect of anesthetics seems to be different in different animal models. We decided to evaluate anesthetics in a well-known model of cerebral ischemia and also in hypotensive models designed by us. We used a model of cerebral ischemia (MCAO) to test anesthetics neuroprotective effect in a two-week period. Then, we used a model of hypotension to characterize the damage caused by this type of insult. Finally we characterized a model of hypotension plus hypoxia that can mimic real situations in the OR.

We found that anesthetics alone do not have a neuroprotective effect after two weeks in the MCAO model; but the combination of anesthetics with caspase inhibitors can decrease the damage caused by ischemia. The caspase inhibitor by itself did not show a significant neuroprotective effect.

We also found that repetitive periods of profound hypotension can cause important damage in the hippocampus but no memory or neurological changes were seen. The induction of only one episode of hypotension plus hypoxia did not alter the morphology of the hippocampus although induced memory changes that were reverted by the use of anesthetics.

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