title: Rapamycin protects against middle cerebral artery occlusion induced focal cerebral ischemia in rats.
abstract: Stroke is a major cause of mortality and disability. The management with thrombolytic therapy has to be initiated within 3-4 h and is associated with limitations like increased risk of intracranial hemorrhage and progression of cerebral injury. Immunophilin inhibitors such as cyclosporine A and tacrolimus have been shown to afford neuroprotection by improving neurological functions and infarct volume in models of ischemic stroke. In the present study, the effect of rapamycin in middle cerebral artery occlusion (MCAo) model of ischemic stroke was evaluated. Ischemic stroke was induced in rats by occluding the MCA using the intraluminal thread. After 1 h of MCAo, animals were administered rapamycin (50, 150, 250 μg/kg, i.p.). After 2 h of occlusion, reperfusion was done. Thirty minutes after reperfusion, animals were subjected to diffusion-weighted magnetic resonance imaging for assessment of protective effect of rapamycin. Twenty-four hours after MCAo, motor performance was assessed, the animals were euthanized and the brains were removed for estimation of malondialdehyde, glutathione, nitric oxide and myeloperoxidase. Significant improvement was observed with rapamycin 150 and 250 μg/kg in percent infarct area, apparent diffusion coefficient and signal intensity as compared to vehicle treated group. Rapamycin treatment ameliorated motor impairment associated with MCAo and significantly reversed the changes in levels of malondialdehyde, glutathione, nitric oxide and myeloperoxidase. The results of the present study indicate neuroprotective effect of rapamycin in MCAo model of stroke. Therefore, rapamycin might be considered as a therapeutic strategy for stroke management.
authors: Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. anjibarak666@gmail.com
authors: Anjali
authors: A
authors: Chauhan
authors: Uma
authors: U
authors: Sharma
authors: N R
authors: NR
authors: Jagannathan
authors: K H
authors: KH
authors: Reeta
authors: Yogendra Kumar
authors: YK
authors: Gupta
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D018737:Hand Strength; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D059906:Neuroimaging / Q000379:methods; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test / Q000379:methods; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione; D020123:Sirolimus