title: Rapamycin ameliorates brain metabolites alterations after transient focal ischemia in rats.
abstract: Rapamycin has been shown to protect against middle cerebral artery occlusion (MCAo) induced ischemic injury. In this study, the neuroprotective effect of rapamycin on the metabolic changes induced by MCAo was evaluated using nuclear magnetic resonance (NMR) spectroscopy of brain tissues. MCAo in rats was induced by insertion of nylon filament. One hour after ischemia, rapamycin (250 µg/kg, i.p.) in dimethyl sulfoxide was administered. Reperfusion was done 2h after ischemia. Twenty-four hours after ischemia phospholipase A2 (PLA2) levels and metabolic changes were assessed. Perchloric acid extraction was performed on the brain of all animals (n=7; sham, vehicle; DMSO and rapamycin 250 µg/kg) and the various brain metabolites were assessed by NMR spectroscopy. In all 44 metabolites were assigned in the proton NMR spectrum of rat brain tissues. In the vehicle group, we observed increased lactate levels and decreased levels of glutamate/glutamine, choline containing compounds, creatine/phosphocreatine (Cr/PCr), taurine, myo-inositol, γ-amino butryic acid (GABA), N-aspartyl aspartate (NAA), purine and pyrimidine metabolites. In rapamycin treated rats, there was increase in the levels of choline containing compounds, NAA, myo-inositol, glutamate/glutamine, GABA, Cr/PCr and taurine as compared to those of vehicle control (P<0.05). Rapamycin treatment reduced PLA2 levels as compared to vehicle group (P<0.05). Our findings indicated that rapamycin reduced the increased PLA2 levels and altered brain metabolites after MCAo. These protective effects might be attributed to its effect on cell membrane metabolism; glutamate induced toxicity and calcium homeostasis in stroke.
authors: Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. Electronic address: chauhananji11@gmail.com.
authors: Anjali
authors: A
authors: Chauhan
authors: Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors: Uma
authors: U
authors: Sharma
authors: Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors: Naranamangalam R
authors: NR
authors: Jagannathan
authors: Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. Electronic address: yk.ykgupta@gmail.com.
authors: Yogendra Kumar
authors: YK
authors: Gupta
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D054467:Phospholipases A2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D054467:Phospholipases A2; D020123:Sirolimus
keywords: Focal cerebral ischemia; Metabolites; Middle cerebral artery occlusion; NMR spectroscopy; Rapamycin; Rapamycin (PubChem CID CAS 53123-88-9)