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

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.

Heterogeneous expression of dopaminergic markers and Vglut2 in mouse mesodiencephalic dopaminergic nuclei A8–A13

“…Western blot performed on brain extracts of mice, rats or humans showed that the AB177487 detects two bands at 45–50 kDA. It has been widely used to label neurons in rat (H. Yu,Wang, et al 2019) or mouse brain slices (Joy et al, 2019; Saito et al, 2018).…”

Neuronal Transmembrane Chloride Transport Has a Time-Dependent Influence on Survival of Hippocampal Cultures to Oxygen-Glucose Deprivation

“…Inducing sedation by enhancing the activity of the GABA A receptor is quite common in stroke patients and it is only sensible to ask whether this pharmacological manipulation could potentially have any detrimental effects on neuronal viability in this setting, especially since literature data are controversial regarding this matter [62][63][64]. It has also been suggested that benzodiazepines may be neuroprotective when given soon after stroke, but harmful when administered during late recovery [63].…”

Network-based drug repurposing for potential stroke therapy

“…Totally, 68 out of them (36.8 %) have been confirmed with anti-stroke effects by in vivo , in vitro or other literature evidence ( Supplementary Table 3 ). Taking midazolam for example, abundant research indicated that midazolam exerted beneficial effects on focal cerebral ischemia in rats via anti-apoptotic mechanisms [39] . Diazepam was also demonstrated to reduce brain lesion size in a photothrombotic rat model of focal ischemia [40] .…”