Imatinib attenuates neurobehavioral deficits and hippocampal neuronal damage after global cerebral ischemia in gerbils.

Abstract

Abstract: Imatinib mesylate, a selective tyrosine kinase inhibitor, exhibited beneficial effects against various neurological diseases besides its anticancer activity. However, its effects on global cerebral ischemia in gerbils remain to be investigated. Global cerebral ischemia was induced by bilateral carotid artery occlusion (BCAO) in male Mongolian gerbils. Imatinib (3, 10, and 30 mg/kg BW) was administered intraperitoneally (i.p.) 30 min before BCAO. Imatinib (3 and 10 mg/kg) significantly ameliorated neurological deficits, locomotor hyperactivity, and cognitive deficits (Y-maze spontaneous alternations) at 4, 24, and 72 h, respectively, after reperfusion in gerbils. Imatinib caused reduction in neuronal cell death in CA1 hippocampal region of gerbils after BCAO and was associated with abrogation of elevated immunoreactivity of endoplasmic reticulum (ER) stress markers (GRP78 and CHOP). This study demonstrates the neuroprotective effect along with functional improvement by imatinib in global cerebral ischemia in gerbils that may be due to mitigation of ER stress.