Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response.
Mild Traumatic Brain Injury-Induced Disruption of the Blood-Brain Barrier Triggers an Atypical Neuronal Response.
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DOI：
10.3389/fncel.2022.821885
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发表时间：
2022
影响因子：
5.3
通讯作者：
Robel S
中科院分区：
文献类型：
--
作者：
Munoz-Ballester C;Mahmutovic D;Rafiqzad Y;Korot A;Robel S
轻度脑外伤每年影响75%的脑外伤幸存者或全球5000多万人，可导致部分患者出现睡眠障碍、认知障碍、情绪波动和创伤后癫痫等后果。要中断这些合并症的进展，识别早期病理事件是关键。最近的研究表明，由机械冲击引起的微出血在mTBI后持续数月，并与更糟糕的mTBI结果相关。然而，mTBI诱导的血脑屏障损伤对神经元的影响尚未揭示。我们使用了一个特征良好的mTBI小鼠模型，该模型表现出频繁而广泛的但大小受限的血脑屏障损伤，以评估神经元在这种病理背景下对暴露于血液传播因素的反应。应用免疫组织化学和组织学方法观察mTBI后兴奋性神经元和抑制性神经元中神经元蛋白的表达。我们观察到，在血脑屏障被破坏的区域，NeuN、小白蛋白和CaMKII的表达在几分钟内就消失了。然而，这些神经元仍然活着，甚至在6个月后也可以用荧光尼氏染色检测到。在没有机械冲击的情况下，由于内皮细胞的消融，神经元暴露于血源性因子后也观察到了类似的表型，这表明血源性因子进入大脑足以诱导神经元的非典型反应。观察到突触后棘的变化表明功能发生了变化。因此，这项研究表明，在没有神经变性的情况下，神经元暴露于血液传播因素会导致神经元蛋白质的快速和持续丢失以及脊柱形态的变化，这一发现可能与许多神经病理学有关。
Mild TBI (mTBI), which affects 75% of TBI survivors or more than 50 million people worldwide each year, can lead to consequences including sleep disturbances, cognitive impairment, mood swings, and post-traumatic epilepsy in a subset of patients. To interrupt the progression of these comorbidities, identifying early pathological events is key. Recent studies have shown that microbleeds, caused by mechanical impact, persist for months after mTBI and are correlated to worse mTBI outcomes. However, the impact of mTBI-induced blood-brain barrier damage on neurons is yet to be revealed. We used a well-characterized mouse model of mTBI that presents with frequent and widespread but size-restricted damage to the blood-brain barrier to assess how neurons respond to exposure of blood-borne factors in this pathological context. We used immunohistochemistry and histology to assess the expression of neuronal proteins in excitatory and inhibitory neurons after mTBI. We observed that the expression of NeuN, Parvalbumin, and CamKII was lost within minutes in areas with blood-brain barrier disruption. Yet, the neurons remained alive and could be detected using a fluorescent Nissl staining even 6 months later. A similar phenotype was observed after exposure of neurons to blood-borne factors due to endothelial cell ablation in the absence of a mechanical impact, suggesting that entrance of blood-borne factors into the brain is sufficient to induce the neuronal atypical response. Changes in postsynaptic spines were observed indicative of functional changes. Thus, this study demonstrates That exposure of neurons to blood-borne factors causes a rapid and sustained loss of neuronal proteins and changes in spine morphology in the absence of neurodegeneration, a finding that is likely relevant to many neuropathologies.
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影响因子：
3.2
作者：
Doherty, Colin P.;O'Keefe, Eoin;Campbell, Matthew
通讯作者：
Campbell, Matthew
DOI：
10.3791/2270
发表时间：
2010-11-16
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Ippolito, Dominic M;Eroglu, Cagla
通讯作者：
Eroglu, Cagla
影响因子：
4.1
作者：
FODA, MAA;MARMAROU, A
通讯作者：
MARMAROU, A
影响因子：
3.6
作者：
Filice F;Vörckel KJ;Sungur AÖ;Wöhr M;Schwaller B
通讯作者：
Schwaller B
影响因子：
30.8
作者：
Cooper, Gregory M.;Coe, Bradley P.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.