Research Information System
PHARMACEUTICAL CHEMISTRY JOURNAL, vol.57, no.6, pp.793-808, 2023 (SCI-Expanded)
Early brain injury (EBI) in the first 24–72 h is the leading cause of mortality and disability related to
subarachnoid hemorrhage (SAH). Both melatonin and microRNAs (miRs) are involved in the regulation of a
number of neuronal molecular signaling procedures in the central nervous system, ranging from hypoxia, inflammation
to neuronal apoptosis. The present study was performed to explore the effect of miRs-17/20 and
combined treatment with melatonin on early brain injury after SAH and underlying molecular mechanisms in
rats. In this study 54 Wistar albino rats were divided into six experimental groups: Sham, SAH,
SAH + Melatonin, SAH+miRs-17/20 control, SAH+MEL+miRs-17/20, and SAH+MEL+miRs-17/20. The
Garcia’s Neurological Scoring Scale and motor coordination tests were used for clinical observation. H&E
staining was performed to evaluate pathological score. The gene expression levels were determined by
qRT-PCR and key proteins were quantitated by Western blot assay. miRs-17/20 with or without melatonin
treatment suppressed the expression and activity of both the HIF1/VEGF/MMPs and the IL6R/JAK2/STAT3
axis. miRs-17/20 with or without melatonin treatment also mitigated the clinical impairment, pyknosis, and
edema in the hippocampus and cortex and neurodegeneration induced by SAH. Our results show that
miRs-17/20 alleviated EBI by reducing hypoxic conditions, hypoxia-induced molecular signaling, and
neuronal apoptosis.