Neuroprotective effects of midazolam on focal cerebral ischemia in rats through anti‑apoptotic mechanisms

Yu,Hang; Wang,Xiaozhi; Kang,Fuxin; Chen,Zhile; Meng,Yunxia; Dai,Mingming

doi:10.3892/ijmm.2018.3973

Neuroprotective effects of midazolam on focal cerebral ischemia in rats through anti‑apoptotic mechanisms

Authors:
- Hang Yu
- Xiaozhi Wang
- Fuxin Kang
- Zhile Chen
- Yunxia Meng
- Mingming Dai
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Affiliations: Intensive Care Unit, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China, Department of Internal Neurology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, P.R. China
Published online on: November 5, 2018 https://doi.org/10.3892/ijmm.2018.3973
Pages: 443-451

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Abstract

Stroke is a cerebrovascular circulatory disorder and its high mortality rate represents a prominent threat to human health. Subsequent apoptosis and cytotoxicity are the main causes underlying the poor prognosis. Midazolam (MDZ) is a benzodiazepine drug that is clinically used during surgical procedures and for the treatment of insomnia, with a potential ability to treat stroke. The protective effect of MDZ was investigated on glutamate‑induced cortical neuronal injuries in vitro and transient middle cerebral artery occlusion (tMCAO) rat models in vivo. Western blot analysis and semi quantitative RT‑PCR were used to evaluate the potential underlying mechanisms. In vitro studies revealed that MDZ regulated apoptosis‑associated gene expression and inhibited lactate dehydrogenase (LDH) release, protecting against neuronal damage. In vivo studies revealed that MDZ reduced LDH‑induced neuronal damage by reducing LDH release from the peripheral blood, and brain tissue staining revealed that MDZ protected neurons during tMCAO. MDZ protected neurons under an ischemic environment by inhibiting LDH release and regulating apoptosis‑associated gene expression to reduce cytotoxicity and apoptosis. These results provide a reliable basis for further studies on the effect of MDZ, to improve the prognosis of cerebral infarction.

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