Morphine pretreatment protects against cerebral ischemic injury via a cPKC[gamma]-mediated anti-apoptosis pathway

• Published in: Experimental and therapeutic medicine Vol. 22; no. 3
• Main Authors: Zhao, Xiao-Yan, Li, Jun-Fa, Li, Tian-Zuo, Pan, Chu-Xiong, Xue, Fu-Shan, Wang, Gu-Yan
• Format: Journal Article
• Language: English
• Published: Spandidos Publications 01.09.2021
• Subjects: Apoptosis; Cellular signal transduction; Cerebral ischemia; Drug therapy; Health aspects; Morphine; Neuroprotective agents; Protein kinases; Testing; China
• DOI: 10.3892/etm.2021.10448
• ISSN: 1792-0981

It has been reported that morphine pretreatment (MP) can exert neuroprotective effects, and that protein kinase C (PKC) participates in the initiation and development of ischemic/hypoxic preconditioning in the brain. However, it remains unknown whether PKC is involved in MP-induced neuroprotection. The aim of the present study, which included in vivo and in vitro experiments, was to determine whether the conventional [gamma] isoform of PKC (cPKC[gamma]) was involved in the protective effects of MP against cerebral ischemic injury. The present study included an in vivo experiment using a mouse model of middle cerebral artery occlusion and an in vitro experiment using neuroblastoma N2a cells with oxygen-glucose deprivation (OGD). Furthermore, a cPKC[gamma] antagonist, Go6983, was used to determine the involvement of cPKC[gamma] in the protective effects of MP against cerebral ischemic injury. In the in vivo experiment, neurological deficits, ischemic infarct volume, neural cell damage, apoptosis and caspase-3 activation were evaluated. In the in vitro experiment, flow cytometry was used to determine the activation of caspase-3 in N2a cells with OGD. It was found that MP protected against cerebral ischemic injury. However, intracerebroventricular injection of the cPKC[gamma] antagonist before MP attenuated the neuroprotective effect of MP and increased the activation of cleaved caspase-3. These findings suggested that MP may provide protection against cerebral ischemic injury via a cPKC[gamma]-mediated anti-apoptosis pathway. Key words: middle cerebral artery occlusion, morphine, mice, neuroprotection, protein kinase C