Open AccessNeuroprotective effects of midazolam on focal cerebral ischemia in rats through anti‑apoptotic mechanisms
Author(s) -
Hang Yu,
Xiaozhi Wang,
Fu-xin Kang,
Zhile Chen,
Yunxia Meng,
Mingming Dai
Publication year - 2018
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2018.3973
Subject(s) - neuroprotection , apoptosis , pharmacology , in vivo , ischemia , glutamate receptor , biology , lactate dehydrogenase , stroke (engine) , cytotoxicity , brain damage , anesthesia , medicine , in vitro , neuroscience , biochemistry , enzyme , receptor , mechanical engineering , microbiology and biotechnology , engineering
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.