Real Time In Vivo Evaluation of Mitochondrial Activity and Brain Functions during Ischemic Stroke

Abstract

More than 50% of total energy consumed by the brain is utilized by active transport processes which are responsible for keeping the ionic homeostasis in the brain. Under an ischemic condition, energy availability is limited, and, as a result, inhibition of the ion pumps is unavoidable. The initial consequence of such inhibition is a gradual accumulation of K+ in the extracellular space leading to a second phase of the ischemic depolarization phenomenon. During ischemic depolarization, extracellular K+ will increase 15-20-fold, while extracellular Ca2+ is decreasing 10 fold. Another optional effect of mild ischemia is the development of Cortical Spreading Depression due to the leakage of K+ into the extracellular space. The Mongolian gerbil provides a very useful animal model to study the effects of ischemia on brain functions. The aims of the study were as follows: (1) To elucidate the mechanism behind the development of ischemic depolarization or cortical spreading depression under unilateral and bilateral carotid artery occlusion. (2) To correlate the kinetics of the recovery processes to the level of ischemia. We tested the correlation between energy depletion level (evaluated by intramitochondrial NADH redox state and Cerebral Blood Flow) and the development of ischemic depolarization or cortical spreading depression (evaluated by extracellular K+, H+, Ca2+, DC potential and 366 nm reflectance changes) under partial and complete ischemia using the multiparametric monitoring system. The results could be summarized as follows: (1) Under bilateral occlusion, in all gerbils the ischemic depolarization was recorded within 1-2 min. (2) Under unilateral occlusion, the level of ischemia obtained was significantly smaller and led to the ischemic depolarization in about 60% of the gerbils. (3) The K+ leakage during the ischemic depolarization had an 'all or none' nature in terms of maximal K÷ levels and time to reach it. (4) The main effect of various lengths of bilateral occlusion was on the recovery time of extracellular K+ level. (5) Cortical spreading depression develop in most cases during the recovery from the ischemic event when ischemic depolarization was not recorded under the ischemic episode.