Nizami Hina Lateef, Srinivasan Krishnamoorthy, Sharma Shyam Sunder
Department of Pharmacology and Toxicology, Molecular Neuropharmacology Laboratory, National Institute of Pharmaceutical Education and Research, Sahibzada Ajit Singh Nagar, Punjab, India.
Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India.
Indian J Pharmacol. 2025 Mar 1;57(2):97-101. doi: 10.4103/ijp.ijp_726_23. Epub 2025 Jun 13.
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.
甲磺酸伊马替尼是一种选择性酪氨酸激酶抑制剂，除了具有抗癌活性外，还对多种神经疾病显示出有益作用。然而，其对沙鼠全脑缺血的影响仍有待研究。通过双侧颈动脉闭塞（BCAO）诱导雄性蒙古沙鼠发生全脑缺血。在BCAO前30分钟腹腔注射（i.p.）伊马替尼（3、10和30mg/kg体重）。在沙鼠再灌注后4、24和72小时，伊马替尼（3和10mg/kg）分别显著改善了神经功能缺损、运动亢进和认知缺陷（Y迷宫自发交替）。伊马替尼可减少BCAO后沙鼠海马CA1区神经元细胞死亡，并与内质网（ER）应激标志物（GRP78和CHOP）免疫反应性升高的消除有关。本研究证明了伊马替尼在沙鼠全脑缺血中具有神经保护作用并能改善功能，这可能是由于减轻了ER应激。
