TRANSIENT FOCAL CEREBRAL ISCHEMIA INDUCED LONG-TERM COGNITIVE FUNCTION DEFICIT IN AN EXPERIMENTAL ISCHEMIC STROKE MODEL

Date

2013-04-12

Authors

Li, Wenjun

ORCID

Journal Title

Journal ISSN

Volume Title

Publisher

Abstract

Purpose: Vascular dementia incorporates cognitive dysfunction with vascular disease, which ranks as the second leading cause of dementia in the United States. However, its underlying pathophysiological mechanism is not fully understood and no effective treatment is available. The purpose of the current study was to evaluate long-term cognitive deficits induced by transient middle cerebral artery occlusion (MCAO) in rats and to investigate the potential underlying mechanism. Methods: Sprague-Dawley rats were subjected to transient MCAO or sham surgery. Behavior tests for locomotor activity and cognitive function were conducted at 7 or 30 days after stroke. Hippocampal long term potentiation (LTP) and involvement of GABAergic signaling were evaluated at 30 days after sham surgery or stroke. Immunohistochemistry and Western blots analysis were conducted to determine the effect of MCAO on cell signaling at the hippocampus. Results: Transient MCAO induced progressive decline of cognitive function. At 30 days after stroke, no neuron loss or synaptic makers change in the hippocampus was observed. Reduction of LTP in both side hippocampus was observed at 30 days after stroke, which could be attenuated by blocking of GABAergic signaling. ERK activation was significantly reduced in both side hippocampus at 30 days after stroke. Conclusions: The present study identified a progressive decline of cognitive function after transient focal cerebral ischemia that correlated with suppression of hippocampal LTP, elevation of GABAergic signaling, and inhibition of ERK activation. Our study indicated that attenuating GABAergic activity or enhancing ERK/MAPK activation in the hippocampus might be potential therapeutic targets to prevent and attenuate cognitive function impairment after ischemic stroke.

Description

Citation

Rights

License