Three dimensional evaluation of cerebrovascular density and branching in chronic traumatic encephalopathy.
Three dimensional evaluation of cerebrovascular density and branching in chronic traumatic encephalopathy.
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DOI：
10.1186/s40478-023-01612-y
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发表时间：
2023-07-25
影响因子：
7.1
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中科院分区：
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--
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慢性创伤性脑病（CTE）是一种与暴露于重复性头部撞击（RHI）有关的神经退行性疾病，其特征是皮层沟深处过度磷酸化的tau蛋白（p-tau）在血管周围积聚。对暴露于RHI的在世运动员的研究，包括脑震荡和非脑震荡的影响，显示出血脑屏障通透性增加，脑血流量减少，血管反应性改变。在神经病理学诊断为CTE的个体中也有血脑屏障异常的报道。为了进一步研究被诊断为CTE的个体和对照组的三维微血管变化，我们使用SHIELD组织处理和被动脱皮来光学清除和标记死后人类背外侧额叶皮层块。用荧光共聚焦显微镜定量测定血管分支密度和分数体积。我们比较了41名男性脑供者的研究结果，死亡年龄31-89岁，平均年龄64岁，包括12名低CTE供者（McKee期I-II）， 13名高CTE供者（McKee期III-IV）和16名年龄和性别匹配的非CTE对照组（7名有RHI暴露，9名没有RHI暴露）。CTE病例的灰质沟血管分支密度明显高于对照组。CTE组的沟回血管分支密度比和分数体积比也高于对照组，CTE组明显高于1。过度磷酸化的tau病理密度与灰质沟分数体积相关。这些发现表明，CTE的背外侧额叶皮层（DLF）沟的血管覆盖和分支增加，与p-tau病理相关。在线版本包含补充材料，可在10.1186/s40478-023-01612-y获得。
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI) and characterized by perivascular accumulations of hyperphosphorylated tau protein (p-tau) at the depths of the cortical sulci. Studies of living athletes exposed to RHI, including concussive and nonconcussive impacts, have shown increased blood–brain barrier permeability, reduced cerebral blood flow, and alterations in vasoreactivity. Blood–brain barrier abnormalities have also been reported in individuals neuropathologically diagnosed with CTE. To further investigate the three-dimensional microvascular changes in individuals diagnosed with CTE and controls, we used SHIELD tissue processing and passive delipidation to optically clear and label blocks of postmortem human dorsolateral frontal cortex. We used fluorescent confocal microscopy to quantitate vascular branch density and fraction volume. We compared the findings in 41 male brain donors, age at death 31–89 years, mean age 64 years, including 12 donors with low CTE (McKee stage I–II), 13 with high CTE (McKee stage III–IV) to 16 age- and sex-matched non-CTE controls (7 with RHI exposure and 9 with no RHI exposure). The density of vessel branches in the gray matter sulcus was significantly greater in CTE cases than in controls. The ratios of sulcus versus gyrus vessel branch density and fraction volume were also greater in CTE than in controls and significantly above one for the CTE group. Hyperphosphorylated tau pathology density correlated with gray matter sulcus fraction volume. These findings point towards increased vascular coverage and branching in the dorsolateral frontal cortex (DLF) sulci in CTE, that correlates with p-tau pathology. The online version contains supplementary material available at 10.1186/s40478-023-01612-y.
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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
影响因子：
48
作者：
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通讯作者：
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影响因子：
5.3
作者：
Bhowmick, Saurav;D'Mello, Veera;Abdul-Muneer, P. M.
通讯作者：
Abdul-Muneer, P. M.
影响因子：
4.8
作者：
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通讯作者：
Pohl, U
影响因子：
4.3
作者：
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