Cerebral ischemia is an important source of morbidity and mortality in a wide variety of brain insults. Current therapy only addresses prevention of ischemia or rehabilitation from infarction because of an incomplete understanding of the processes mediating the progression of ischemic brain to infarction. While completely ischemic brain rapidly infarcts in clinical cases, large regions of incomplete ischemia exist which may proceed to recovery or infarction. Regions of incomplete ischemia are also important for their metabolic activity. Ischemia stimulates the generation of substances such as arachidonate metabolites which could accelerate infarction by compromising microcirculation, altering platelet formation or enhancing ischemic edema formation. However, this metabolism is oxidative and energy requiring therefore requiring some prevention or reconstitution of blood flow. Transient dense cerebral ischemia with reperfusion in the Mongolian gerbil and permanent middle cerebral artery occlusion in the cat will be studied comparing a transient densely ischemic area with a permanent partially ischemic region based on incomplete collaterals. Physiologic parameters will include Hydrogen clearance cerebral blood flow, ischemic edema formation and somatosensory evoked potential changes as well as blood pressure, temperature, arterial blood gases and intracranial pressure. These will be correlated over time with the development of potentially vasoactive or edematogenic derivatives of arachidonic acid and polyamine metabolic pathways. Polyamines are postulated to possess a regulatory function in arachidonate metabolism and vasogenic edema formation. This will be tested within these models by pretreatment with difluromethyl ornithine an inhibitor of polyamine formation. In this way a foundation for further studies of the evolution of cerebral infarction may be developed and the potential for slowing this process by inhibiting the contribution of harmful metabolites may be studied.
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| Dempsey, R J; Baskaya, M K; Combs, D J et al. (1996) Delayed hyperglycemia and intracellular acidosis during focal cerebral ischemia in cats. Acta Neurochir (Wien) 138:745-51 |
