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创伤性小脑损伤模型

Models of traumatic cerebellar injury.

作者信息

Potts Matthew B, Adwanikar Hita, Noble-Haeusslein Linda J

机构信息

Department of Neurological Surgery, University of California, Brain and Spinal Injury Center, San Francisco, CA 94143, USA.

出版信息

Cerebellum. 2009 Sep;8(3):211-21. doi: 10.1007/s12311-009-0114-8. Epub 2009 Jun 5.

Abstract

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Studies of human TBI demonstrate that the cerebellum is sometimes affected even when the initial mechanical insult is directed to the cerebral cortex. Some of the components of TBI, including ataxia, postural instability, tremor, impairments in balance and fine motor skills, and even cognitive deficits, may be attributed in part to cerebellar damage. Animal models of TBI have begun to explore the vulnerability of the cerebellum. In this paper, we review the clinical presentation, pathogenesis, and putative mechanisms underlying cerebellar damage with an emphasis on experimental models that have been used to further elucidate this poorly understood but important aspect of TBI. Animal models of indirect (supratentorial) trauma to the cerebellum, including fluid percussion, controlled cortical impact, weight drop impact acceleration, and rotational acceleration injuries, are considered. In addition, we describe models that produce direct trauma to the cerebellum as well as those that reproduce specific components of TBI including axotomy, stab injury, in vitro stretch injury, and excitotoxicity. Overall, these models reveal robust characteristics of cerebellar damage including regionally specific Purkinje cell injury or loss, activation of glia in a distinct spatial pattern, and traumatic axonal injury. Further research is needed to better understand the mechanisms underlying the pathogenesis of cerebellar trauma, and the experimental models discussed here offer an important first step toward achieving that objective.

摘要

创伤性脑损伤(TBI)是全球发病和死亡的主要原因。对人类TBI的研究表明,即使最初的机械性损伤作用于大脑皮层,小脑有时也会受到影响。TBI的一些症状,包括共济失调、姿势不稳、震颤、平衡和精细运动技能受损,甚至认知缺陷,可能部分归因于小脑损伤。TBI的动物模型已开始探索小脑的易损性。在本文中,我们回顾了小脑损伤的临床表现、发病机制和潜在机制,重点介绍了用于进一步阐明TBI这一了解甚少但重要方面的实验模型。我们考虑了对小脑进行间接(幕上)创伤的动物模型,包括液压冲击、控制性皮质撞击、重物坠落撞击加速和旋转加速损伤。此外,我们还描述了对小脑造成直接创伤的模型,以及重现TBI特定组成部分的模型,包括轴突切断、刺伤、体外拉伸损伤和兴奋性毒性。总体而言,这些模型揭示了小脑损伤的显著特征,包括区域特异性浦肯野细胞损伤或丧失、以独特空间模式激活的胶质细胞,以及创伤性轴突损伤。需要进一步研究以更好地理解小脑创伤发病机制的潜在机制,本文讨论的实验模型为实现这一目标迈出了重要的第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a178/2734258/d6db89d0c6d2/12311_2009_114_Fig1_HTML.jpg

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