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创伤性脑损伤可控皮质撞击损伤模型不同轨迹的脑区特异性组织病理学效应

Brain Region-Specific Histopathological Effects of Varying Trajectories of Controlled Cortical Impact Injury Model of Traumatic Brain Injury.

作者信息

Pabón Mibel M, Acosta Sandra, Guedes Vivian A, Tajiri Naoki, Kaneko Yuji, Borlongan Cesar V

机构信息

Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida College of Medicine, Tampa, FL, USA.

出版信息

CNS Neurosci Ther. 2016 Mar;22(3):200-11. doi: 10.1111/cns.12485. Epub 2016 Jan 18.

Abstract

AIMS

Traumatic brain injury (TBI) occurs when the head is impacted by an external force causing either a closed or penetrating head injury through a direct or accelerating impact. In laboratory research, most of the TBI animal models focus on a specific region to cause brain injury, but traumatic injuries in patients do not always impact the same brain regions. The aim of this study was to examine the histopathological effects of different angles of mechanical injury by manipulating the trajectory of the controlled cortical impact injury (CCI) model in adult Sprague-Dawley rats.

METHODS

The CCI model was manipulated as follows: conventional targeting of the frontal cortex, farthest right angle targeting the frontal cortex, closest right angle targeting the frontal cortex, olfactory bulb injury, and cerebellar injury. Three days after TBI, brains were harvested to analyze cortical and hippocampal cell loss, neuroinflammatory response, and neurogenesis via immunohistochemistry.

RESULTS

Results revealed cell death in the M1 region of the cortex across all groups, and in the CA3 area from olfactory bulb injury group. This observed cell death involved upregulation of inflammation as evidenced by rampant MHCII overexpression in cortex, but largely spared Ki-67/nestin neurogenesis in the hippocampus during this acute phase of TBI.

CONCLUSION

These results indicate a trajectory-dependent injury characterized by exacerbation of inflammation and different levels of impaired cell proliferation and neurogenesis. Such multiple brain areas showing varying levels of cell death after region-specific CCI model may closely mimic the clinical manifestations of TBI.

摘要

目的

当头部受到外力撞击,通过直接或加速冲击导致闭合性或穿透性头部损伤时,就会发生创伤性脑损伤(TBI)。在实验室研究中,大多数TBI动物模型聚焦于特定区域以造成脑损伤,但患者的创伤性损伤并不总是影响相同的脑区。本研究的目的是通过操纵成年Sprague-Dawley大鼠的控制性皮质撞击损伤(CCI)模型的轨迹,来研究不同角度机械损伤的组织病理学效应。

方法

CCI模型的操纵如下:额叶皮质的传统靶向、额叶皮质的最右角度靶向、额叶皮质的最左角度靶向、嗅球损伤和小脑损伤。TBI后三天,取脑通过免疫组织化学分析皮质和海马体中的细胞损失、神经炎症反应和神经发生。

结果

结果显示,所有组的皮质M1区域以及嗅球损伤组的CA3区域均有细胞死亡。这种观察到的细胞死亡涉及炎症上调,皮质中MHCII的过度表达就是证明,但在TBI的急性期,海马体中的Ki-67/巢蛋白神经发生在很大程度上未受影响。

结论

这些结果表明存在一种轨迹依赖性损伤,其特征为炎症加剧以及细胞增殖和神经发生受损程度不同。在区域特异性CCI模型后,多个脑区出现不同程度的细胞死亡,这可能与TBI的临床表现非常相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe0f/6492827/35bf46d2beb4/CNS-22-200-g001.jpg

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