中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (12): 2409-2410.doi: 10.4103/1673-5374.313029

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

开放时间晚：创伤性脑损伤后的神经元膜破坏

  

  • 出版日期:2021-12-15 发布日期:2021-05-14

Open late: neuronal membrane disruption late in traumatic brain injury

Martina L. Hernandez, MiJin Cho, Audrey D. Lafrenaye*   

  1. Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA
  • Online:2021-12-15 Published:2021-05-14
  • Contact: Audrey D. Lafrenaye, PhD,audrey.lafrenaye@vcuhealth.org.
  • Supported by:
    This work was supported by the National Institutes of Health-National Institute of Neurological Disorders and Stroke grant (No. 1R01NS096143).

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摘要：

Neural Regen Res：创伤性脑损伤后神经元膜破裂扩大了潜在的治疗窗口

    细胞膜破裂是一种病理现象，指细胞抵御细胞外环境的主要屏障被破坏。受其影响，一些神经元细胞死亡，而另一些则表现出延迟性破坏，这就为治疗干预提供了机会。通过注入细胞不渗透示踪剂，如右旋糖酐、钙黄质和碘化丙啶，显微镜下才能够观察到其病理变化，因此临床上对膜破裂知之甚少。然而，在各种创伤性脑损伤的临床前模型中，膜破裂已被充分证明。

来自美国弗吉尼亚联邦大学的Audrey D. Lafrenaye团队使用Sprague-Dawley大鼠中央液压冲击损伤（CFPI）模型评估弥漫性脑外伤后膜破裂的扩展时间分布，第一次证明神经元膜在损伤后数周内破裂。对脑损伤引起的膜破裂后的二次波识别大大增加了对膜破裂干预和治疗的潜在治疗窗口，从数小时到数周甚至更久。此外，在CFPI后1周，膜破裂神经元百分比与假手术组比较无显著性差异，这表明膜重新封闭的时间点比之前认为的要晚得多。 Lafrenaye团队强调创伤性脑损伤后神经元膜破裂的异质性超出了机械操作的范围，并比之前预期的进一步扩大了这种病理的潜在治疗窗口。膜破裂通过广泛的损伤后时间框架表现出双相性，并涉及表型不同的亚群，特别是与损伤后的NeuN表达相关。重要的是，在急性和晚期膜破裂人群中，神经元膜修复能力持续改善，可以作为治疗干预的框架。对神经元完整性破坏的深入了解有利于开发新的治疗方法，减少与弥漫性病理相关的发病率。

文章在《中国神经再生研究（英文版）》杂志2021年12月12期发表。

https://orcid.org/0000-0001-5986-2228(Audrey D. Lafrenaye)

Abstract: Membrane disruption is a pathology in which the cellular phospholipid bilayer, which is the cell’s primary defense from the extracellular environment, is compromised. Some neurons that are impacted by membrane disruption experience cell death, and others demonstrate delayed disruption, providing an opportunity for therapeutic intervention. This pathology is visualized using infusions of cell impermeable tracers, such as dextran, calcein and propidium iodide followed by microscopic analysis (Geddes et al., 2003a, b; Singleton and Povlishock, 2004; Farkas et al., 2006; Whalen et al., 2008; Cullen et al., 2011; Lafrenaye et al., 2014; Levine et al., 2016; Hernandez et al., 2019; LaPlaca et al., 2019; Prado and LaPlaca, 2020), and therefore little is known about membrane disruption clinically. However, membrane disruption has been well documented to occur in various pre-clinical models of traumatic brain injury (TBI).