Intranasal miRNAs-17/20 Administration Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats
Pharmaceutical Chemistry Journal, cilt.57, sa.6, ss.793-808, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 57 Sayı: 6
- Basım Tarihi: 2023
- Doi Numarası: 10.1007/s11094-023-02953-7
- Dergi Adı: Pharmaceutical Chemistry Journal
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core
- Sayfa Sayıları: ss.793-808
- Anahtar Kelimeler: melatonin, microRNAs-17/20, subarachnoid hemorrhage early brain injury
- Trakya Üniversitesi Adresli: Evet
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.