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使用清醒闭合性颅脑损伤轻度创伤性脑损伤模型评估突触可塑性的变化。

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury.

机构信息

Division of Medical Sciences, University of Victoria; Island Medical Program, University of British Columbia;

Division of Medical Sciences, University of Victoria.

出版信息

J Vis Exp. 2023 Jan 20(191). doi: 10.3791/64592.

Abstract

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of closed-head mTBI in the preclinical setting to increase translatability to the clinical population. The awake closed-headed injury (ACHI) model uses a modified controlled cortical impactor to deliver closed-headed injury, inducing clinically relevant behavioral deficits without the need for a craniotomy or the use of an anesthetic. This technique does not normally induce fatalities, skull fractures, or brain bleeds, and is more consistent with being a mild injury. Indeed, the mild nature of the ACHI procedure makes it ideal for studies investigating repetitive mTBI (r-mTBI). Growing evidence indicates that r-mTBI can result in a cumulative injury that produces behavioral symptoms, neuropathological changes, and neurodegeneration. r-mTBI is common in youths playing sports, and these injuries occur during a period of robust synaptic reorganization and myelination, making the younger population particularly vulnerable to the long-term influences of r-mTBI. Further, r-mTBI occurs in cases of intimate partner violence, a condition for which there are few objective screening measures. In these experiments, synaptic function was assessed in the hippocampus in juvenile rats that had experienced r-mTBI using the ACHI model. Following the injuries, a tissue slicer was utilized to make hippocampal slices to evaluate bidirectional synaptic plasticity in the hippocampus at either 1 or 7 days following the r-mTBI. Overall, the ACHI model provides researchers with an ecologically valid model to study changes in synaptic plasticity following mTBI and r-mTBI.

摘要

轻度创伤性脑损伤(mTBI)是北美地区普遍存在的健康问题。在临床前环境中,利用具有生态有效性的闭合性颅脑 mTBI 模型来提高对临床人群的转化能力的压力越来越大。清醒闭合性颅脑损伤(ACHI)模型使用改良的皮质控制撞击器来造成闭合性颅脑损伤,在不需要开颅手术或使用麻醉剂的情况下,诱导出具有临床相关性的行为缺陷。该技术通常不会导致死亡、颅骨骨折或脑出血,并且更符合轻度损伤的情况。事实上,ACHI 程序的轻度性质使其成为研究重复性 mTBI(r-mTBI)的理想选择。越来越多的证据表明,r-mTBI 可能导致累积性损伤,从而产生行为症状、神经病理学变化和神经退行性变。r-mTBI 在从事运动的年轻人中很常见,这些损伤发生在突触重组和髓鞘形成的活跃时期,使年轻人群特别容易受到 r-mTBI 的长期影响。此外,r-mTBI 发生在亲密伴侣暴力的情况下,这种情况几乎没有客观的筛选措施。在这些实验中,使用 ACHI 模型评估了经历 r-mTBI 的幼年大鼠海马中的突触功能。在受伤后,使用组织切片机制作海马切片,以评估 r-mTBI 后 1 天或 7 天海马中的双向突触可塑性。总体而言,ACHI 模型为研究人员提供了一种具有生态有效性的模型,用于研究 mTBI 和 r-mTBI 后突触可塑性的变化。

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