Drug Design, Development and Therapy (Feb 2019)
Neuroprotective potential of ketamine prevents developing brain structure impairment and alteration of neurocognitive function induced via isoflurane through the PI3K/AKT/GSK-3β pathway
Abstract
Ruiwei Wang,1,* Zihao Zhang,2,* Mukesh Kumar,3 Guangming Xu,4 Mengyuan Zhang1 1Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province 250021, People’s Republic of China; 2Department of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province 330031, People’s Republic of China; 3Radhagovind College, Moradabad 204411, India; 4Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province 250021, People’s Republic of China *These authors contributed equally to this work Background: The aim of the current experimental study was to scrutinize the neuroprotective effect of ketamine on the isoflurane (iso)-induced cognitive dysfunction in rats via phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK-3β) pathway. Materials and methods: Sprague-Dawley rats were used for the current experimental study. The rats were divided into six groups and rats were treated with ketamine and memantine. For the estimation of cognitive function study, we used the Morris water test. Pro-inflammatory cytokines such as IL-1β, IL-6, tumor necrosis factor-α (TNF-α), and caspase-6; the antioxidant parameters malondialdehyde, glutathione, superoxide dismutase, catalase, and protein carbonyl; acetylcholinesterase, amyloid β, and brain-derived neurotrophic factor were estimated, respectively. The protein expression of AKT, GSK-3β, p21WAF1/CIP1, and p53 was also estimated, respectively. Results: Ketamine significantly enhanced cognitive function and showed anti-inflammatory and antioxidant effects, and exhibited the neuroprotective effect of ketamine against the isoflurane-induced cognitive impairment. Additionally, ketamine significantly (P<0.005) suppressed IL-1β, TNF-α, IL-6, caspase-6 and p21WAF1/CIP1, p53 expression and up-regulated the PI3K/AKT/GSK-3β expression in the group of iso-induced rats. Conclusion: We can conclude that ketamine prevented the cognitive impairment induced by isoflurane anesthesia through anti-apoptotic, anti-inflammatory, and antioxidant effects via the PI3K/AKT/GSK-3β pathway. Keywords: ketamine, isoflurane, neuroinflammatory, PI3K/AKT/GSK-3β pathway, cognitive impairment
