Abstract
Ischemic stroke is one of the most dangerous acute diseases which causes death or deformity. Apoptosis has been shown to play an important role in the development and pathogenesis of cerebral ischemia–reperfusion injury (I/R injury), but the related mechanism is unclear. Levo-tetrahydropalmatine (l-THP), a bioactive ingredient extracted from the Chinese herb Corydalis, can penetrate the blood–brain barrier and exert various pharmacological effects on neural tissues. The present study examined the neuroprotective effect of l-THP on neuronal apoptosis induced by cerebral I/R injury. Results showed that pretreatment with l-THP (12.5, 25, and 50 mg/kg) improved neurological outcomes and reduced infarct volume and cerebral edema in comparison with the brains of the middle cerebral artery occlusion (MCAO) group. These findings provided evidence for the neuroprotective effects of l-THP against cerebral I/R injury. Furthermore, administration of l-THP enhanced the expression of Bcl-2 and attenuated the content of Bax, cleaved caspase-3, and PARP. l-THP could improve the reduction of NeuN-positive cells induced by I/R injury. These results suggested that l-THP could inhibit neuroapoptosis in cerebral ischemic rats. c-Abl was discovered as the critical protein responsible for neurocyte apoptosis; however, few data have been published on the relation between ischemic stroke and the expression of c-Abl. We found that both c-Abl expression and neuronal apoptosis were significantly increased in the MCAO group, while pretreatment with l-THP could ameliorate this effect. Therefore, we deduced that reduced c-Abl overexpression may play a role in the anti-apoptosis effect of l-THP after cerebral I/R injury. Thus, l-THP may provide a potential therapeutic approach for the treatment of ischemic stroke.
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Abbreviations
- I/R:
-
Ischemia/reperfusion
- l-THP:
-
Levo-tetrahydropalmatine
- MCAO:
-
Middle cerebral artery occlusion
- TTC:
-
Triphenyltetrazolium chloride
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This research is supported by Chinese Nature Science Foundation (81573701), China Postdoctoral Science Foundation (2017 M611958), and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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The protocol was approved by the Animal Ethics Committee of China Pharmaceutical University and was in agreement with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
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Sun, R., Song, Y., Li, S. et al. Levo-tetrahydropalmatine Attenuates Neuron Apoptosis Induced by Cerebral Ischemia–Reperfusion Injury: Involvement of c-Abl Activation. J Mol Neurosci 65, 391–399 (2018). https://doi.org/10.1007/s12031-018-1063-9
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DOI: https://doi.org/10.1007/s12031-018-1063-9