Therapeutic effect of and mechanisms underlying the effect of miR-195-5p on subarachnoid hemorrhage-induced vasospasm and brain injury in rats

PeerJ

article

Tai-Hsin Tsai¹  Chih-Hui Chang¹  Szu-Huai Lin⁴  Yu-Feng Su¹  Yi-Cheng Tsai¹  Sheau-Fang Yang⁵  Chih-Lung Lin¹ 

[1] Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital;Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University;Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University;Department of Nursing, Kaohsiung Medical University Hospital;Department of Pathology, Kaohsiung Medical University Hospital;Department of Pathology, School of Medicine, College of Medicine, Kaohsiung Medical University

关键词: Subarachnoid hemorrhage;    Cerebral vasospasm;    Apoptosis;    iNOS;    eNOS;    miR-195-5p;    TNF-α;    NF-κB;   

DOI  :  10.7717/peerj.11395

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

ObjectivesThere is much evidence suggesting that inflammation contributes majorly to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and brain injury. miRNAs have been found to modulate inflammation in several neurological disorders. This study investigated the effect of miR-195-5p on SAH-induced vasospasm and early brain injury in experimental rats.MethodsNinety-six Sprague-Dawley male rats were randomly and evenly divided into a control group (no SAH, sham surgery), a SAH only group, a SAH + NC-mimic group, and a SAH + miR-195-5p group. SAH was induced using a single injection of blood into the cisterna magna. Suspensions containing NC-mimic and miR-195-5p were intravenously injected into rat tail 30 mins after SAH was induced. We determined degree of vasospasm by averaging areas of cross-sections the basilar artery 24h after SAH. We measured basilar artery endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κ B), phosphorylated NF-κ B (p-NF-κ B), inhibitor of NF-κ B (Iκ Bα) and phosphorylated-Iκ Bα (p-Iκ Bα). Cell death assay was used to quantify the DNA fragmentation, an indicator of apoptotic cell death, in the cortex, hippocampus, and dentate gyrus. Tumor necrosis factor alpha (TNF-α) levels were measured using sample protein obtained from the cerebral cortex, hippocampus and dentate gyrus.ResultsPrior to fixation by perfusion, there were no significant physiological differences among the control and treatment groups. SAH successfully induced vasospasm and early brain injury. MiR-195-5p attenuated vasospasam-induced changes in morphology, reversed SAH-induced elevation of iNOS, p-NF-κ B, NF-κ B, and p-Iκ Bα and reversed SAH-induced suppression of eNOS in the basilar artery. Cell death assay revealed that MiR-195-5p significantly decreased SAH-induced DNA fragmentation (apoptosis) and restored TNF-α level in the dentate gyrus.ConclusionIn conclusion, MiRNA-195-5p attenuated SAH-induced vasospasm by up-regulating eNOS, down-regulating iNOS and inhibiting the NF-κ B signaling pathway. It also protected neurons by decreasing SAH-induced apoptosis-related cytokine TNF-α expression in the dentate gyrus. Further study is needed to elucidate the detail mechanism underlying miR-195-5p effect on SAH-induced vasospasm and cerebral injury. We believe that MiR-195-5p can potentially be used to manage SAH-induced cerebral vasospasm and brain injury.

【 授权许可】

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