Abstract

Objective: Previously we have found that stroke by distal occlusion of the middle cerebral artery (dMCAO) produced injury restricted to the parietal cortex yet hippocampal impairment. Recent advances in functional connectivity suggest that shared neuronal activation patterns or synchronized brain oscillation define brain networks linking anatomically separate brain regions. Using in vivo electrophysiology, the current study aimed to determine the temporal profile of stroke-induced changes in brain oscillation in the hippocampus, a remote brain region that does not suffer from ischemic injury. Methods: Adult male rats were subjected to either a permanent left MCAO combined with a temporary bilateral occlusion of the common carotid artery (CCAO), or bilateral CCAO alone, for 1 hour. Bilateral extracellular recording was performed under urethane anesthesia using the 32-channel NeuroNexus probes spanning the cortex and CA1 radiatum layer. Results: During reperfusion, a significant decrease in theta-to-delta ratio (T/D) was observed in rats that underwent either dMCAO or CCAO alone. However, a sustained delta predominant state was only observed chronically after dMCAO, suggesting a persistent disruption of hippocampal-neocortical connectivity in the former. In contrast to CCAO, dMCAO also induced a reduced low gamma (30-59 Hz) power, change in dominant theta-frequency and disassociation of theta-gamma coupling. Conclusions: Our results indicate that ischemic stroke induces specific changes in hippocampal oscillations that might underlie the observed cognitive impairment. In contrast to stroke, an episode of mild ischemia by temporary CCAO that does not trigger functional impairment also does not evoke persistent changes in hippocampal oscillations. The observed brain oscillation profile specific to dMCAO offers an integrated measurement of the hippocampal-dependent network activity, and may serve as a candidate biomarker for post-stroke cognitive impairment.

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