INTRANASAL MIRNAS-17/20 ADMINISTRATION ALLEVIATE EARLY BRAIN INJURY AFTER SUBARACHNOID HEMORRHAGE IN RATS

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Malçok Ü. A., Doğanlar O., Tüfekçioğlu N. K., Ovalı M. A., Aykora D., Doğanlar Z. B., ...Daha Fazla

PHARMACEUTICAL CHEMISTRY JOURNAL, cilt.57, sa.6, ss.793-808, 2023 (SCI-Expanded)

  • 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
  • Çanakkale Onsekiz Mart 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.