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

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....

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Bibliographic Details
Published inExperimental 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
LanguageEnglish
Published Spandidos Publications 01.09.2021
Subjects
Apoptosis
Cellular signal transduction
Cerebral ischemia
Drug therapy
Health aspects
Morphine
Neuroprotective agents
Protein kinases
Testing
China
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Summary: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
ISSN:1792-0981
DOI:10.3892/etm.2021.10448