Intranasal miRNAs-17/20 Administration Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats
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Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
subarachnoid hemorrhage early brain injury, microRNAs-17/20, melatonin
Kaynak
Pharmaceutical Chemistry Journal
WoS Q Değeri
Q4
Scopus Q Değeri
Q4
Cilt
57
Sayı
6
