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中风后全身振动疗法改变大脑转录组以促进中年雌性大鼠的缺血耐受。

Post-stroke whole body vibration therapy alters the cerebral transcriptome to promote ischemic tolerance in middle-aged female rats.

机构信息

Peritz Scheinberg Cerebral Vascular Disease Research Laboratories (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Neuroscience Graduate Program, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL, 33136, USA.

Miami Project to Cure Paralysis, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Department of Neurological Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Neuroscience Graduate Program, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA; Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL, 33136, USA.

出版信息

Neurochem Int. 2024 Nov;180:105843. doi: 10.1016/j.neuint.2024.105843. Epub 2024 Aug 28.

Abstract

Low-frequency whole body vibration (WBV; 40 Hz) therapy after stroke reduces ischemic brain damage, motor, and cognitive deficits in middle-aged rats of both sexes. However, the underlying mechanisms responsible for WBV induced ischemic protections remain elusive. In the current study, we hypothesize that post-stroke WBV initiates transcriptional reprogramming in the cortex of middle-aged female rats which is responsible for the observed reduced stroke consequences. Middle-aged female Sprague-Dawley rats that remained in constant diestrus (reproductively senescent) were randomized to either sham or transient middle cerebral artery occlusion (tMCAO; 90 min) surgery. A day after induction of tMCAO, animals received either WBV or no-WBV treatment for 15 min twice a day for five days for a week. Post-treatment, cortical tissue was analyzed for gene expression using RNA sequencing (RNAseq) and gene enrichment analysis via Enrichr. The RNAseq data analysis revealed significant changes in gene expression due to WBV therapy and the differentially expressed genes are involved in variety of biological processes like neurogenesis, angiogenesis, excitotoxicity, and cell death. Specifically, observed significant up-regulation of 116 and down-regulation of 258 genes after WBV in tMCAO exposed rats as compared to the no-WBV group. The observed transcriptional reprogramming will identify the possible mechanism(s) responsible for post-stroke WBV conferred ischemic protection and future studies will be needed to confirm the role of the genes identified in the current study.

摘要

低频全身振动(WBV;40 Hz)治疗中风后可减少中年雄性和雌性大鼠的缺血性脑损伤、运动和认知缺陷。然而,导致 WBV 诱导的缺血性保护的潜在机制仍不清楚。在目前的研究中,我们假设中风后 WBV 会启动中年雌性大鼠皮质中的转录重编程,这是观察到的中风后果减少的原因。处于持续发情期(生殖衰老)的中年雌性 Sprague-Dawley 大鼠被随机分为假手术或短暂性大脑中动脉闭塞(tMCAO;90 分钟)手术组。tMCAO 诱导后一天,动物接受 WBV 或无 WBV 治疗,每天两次,每次 15 分钟,持续 5 天,共 1 周。治疗后,使用 RNA 测序(RNAseq)分析皮质组织的基因表达,并使用 Enrichr 进行基因富集分析。RNAseq 数据分析显示,WBV 治疗导致基因表达发生显著变化,差异表达的基因涉及多种生物学过程,如神经发生、血管生成、兴奋性毒性和细胞死亡。具体来说,与无 WBV 组相比,tMCAO 暴露大鼠接受 WBV 后观察到 116 个基因显著上调,258 个基因下调。观察到的转录重编程将确定中风后 WBV 诱导的缺血性保护的可能机制,并需要进一步的研究来确认本研究中鉴定的基因的作用。

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