Remote limb ischemic post conditioning during early reperfusion alleviates cerebral ischemic reperfusion injury via GSK-3β/CREB/ BDNF pathway.
Remote limb ischemic post conditioning (RIPOC) has been reported to attenuate cerebral ischemic reperfusion (I/R) injury, while the molecular mechanisms remain elusive. Various studies have highlighted the involvement of glycogen synthase kinase (GSK-3β) in cerebral I/R injury and cognitive disorders. Hence, the present study was designed to explore the role of GSK-3β and its downstream regulators in RIPOC mediated neuroprotection against cerebral I/R injury and associated cognitive impairment. Male Wistar rats are randomly assigned into four groups: Sham, bilateral common carotid arteries occlusion (BCCAO), RIPOC and BCCAO+RIPOC. BCCAO was achieved by transient occlusion of bilateral common carotid arteries for 20min, followed by reperfusion. Non-invasive RIPOC was induced by 3 cycles each of 10min occlusion and reperfusion of both femoral arteries by using tourniquets, during early reperfusion phase. A battery of behavioral and cognitive tests were performed. Biochemical estimation of oxidative markers, anti-oxidants and pro-inflammatory markers were estimated. Levels of GSK-3β, CREB and BDNF were estimated to confirm the molecular mechanism. Hippocampal structural abnormalities were confirmed by H and E staining. The neurobehavioral analysis revealed that neurological and cognitive deficits caused by BCCAO, were reduced by RIPOC intervention. Meanwhile, the results of biochemical tests suggested that RIPOC attenuates the BCCAO induced oxidative damage, neuroinflammation and hippocampal structural abnormalities. Further, RIPOC prevented the elevation of BCCAO induced GSK-3β. RIPOC exerts neuroprotective effect against I/R injury, putatively by attenuating GSK-3β expression and upregulating the levels of CREB and BDNF.
Laboratory of Neuropharmacology, Department of Pharmacy, BITS Pilani, Pilani campus, Rajasthan 333031, India.
Sruthi
S
Ramagiri
Laboratory of Neuropharmacology, Department of Pharmacy, BITS Pilani, Pilani campus, Rajasthan 333031, India. Electronic address: taliyanraja@gmail.com.
Rajeev
R
Taliyan
D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005121:Extremities / Q000098:blood supply*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006624:Hippocampus / Q000473:pathology; D057775:Ischemic Postconditioning; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D000071679:Glycogen Synthase Kinase 3 beta
Bilateral common carotid artery occlusion; Cerebral stroke; Cognitive impairment; GSK-3β; Remote limb ischemic post conditioning