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. 2025 Mar 1;57(2):97-101.
doi: 10.4103/ijp.ijp_726_23. Epub 2025 Jun 13.

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

Hina Lateef Nizami  1 , Krishnamoorthy Srinivasan  1   2 , Shyam Sunder Sharma  1
Affiliations

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

Hina Lateef Nizami et al. Indian J Pharmacol. .

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.

Keywords: Endoplasmic reticulum stress; global cerebral ischemia; imatinib; neurobehavioral deficit; neuronal damage; neuroprotection.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Effect of imatinib on neurological, locomotor, and cognitive deficits after global cerebral ischemia in gerbils. (a) Experimental design. (b) Neurological score 4 h after bilateral carotid artery occlusion (BCAO). (c) Ambulatory counts 24 h after BCAO. (d) Ambulatory time 24 h after BCAO. (e) Y-maze relative alternation 72 h after BCAO. Data were represented as median for neurological score and mean ± standard error of mean for ambulatory counts, ambulatory time, and Y-maze alternations (n = 7–8). ***P < 0.001 versus sham group. #P < 0.05, ##P < 0.01, ###P < 0.001 versus ischemia/reperfusion + vehicle group
Figure 2
Figure 2
Effect of imatinib on neuronal damage after global cerebral ischemia in gerbils. Representative photomicrographs of the hippocampal CA1 region of experimental gerbils (n = 3). Arrows indicate neuronal damage. The micron bar indicates 50 μm
Figure 3
Figure 3
Effect of imatinib on endoplasmic reticulum stress markers after global cerebral ischemia in gerbils. (a) Representative photomicrographs of the GRP78-immunostained hippocampal CA1 region of experimental gerbils (n = 3). Arrows indicate GRP immunoreactivity. The micron bar indicates 50 μm. (b) Representative photomicrographs of the CHOP-immunostained hippocampal CA1 region of experimental gerbils (n = 3). Arrows indicate CHOP immunoreactivity. The micron bar indicates 50 μm
See this image and copyright information in PMC

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