Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.
Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.
复制标题
磷酸化的tau是慢性创伤性脑病所独有的吗？癫痫大脑和慢性创伤性脑病中的磷酸化tau。
DOI：
10.1016/j.brainres.2015.11.007
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发表时间：
2016-01-01
期刊：
影响因子：
2.9
通讯作者：
Janigro D
中科院分区：
文献类型：
--
作者：
Puvenna V;Engeler M;Banjara M;Brennan C;Schreiber P;Dadas A;Bahrami A;Solanki J;Bandyopadhyay A;Morris JK;Bernick C;Ghosh C;Rapp E;Bazarian JJ;Janigro D
重复性创伤性脑损伤（Repetitive traumatic brain injury，rTBI）是导致脑内磷酸化tau蛋白（phosphorylated tau，PT）异常沉积和慢性创伤性脑病（chronic traumatic encephalopathy，CTE）的主要危险因素之一。CTE和颞叶癫痫（TLE）影响边缘系统，但没有PT分布在TLE和CTE的比较研究。目前还不清楚PT病理是否由重复头部撞击（rTBI）引起。这些差距阻碍了对PT的发病机制和临床意义的深入了解，限制了我们开发预防和治疗干预措施的能力。我们量化了TLE和CTE中的PT，以揭示rTBI史是否是PT在脑中蓄积的先决条件。将6例尸检CTE（平均73.3岁）和年龄匹配的对照样本与19例手术切除的TLE脑标本（4个月-58岁;平均27.6岁）进行比较。TLE或对照组无TBI病史;所有CTE患者均有rTBI病史。免疫组化显示TLE和CTE脑组织PT水平升高。未观察到年龄依赖性变化，因为PT早在出生后4个月就存在。在TLE和CTE中，皮质神经元、穿透软脑膜血管周围的血管周围区域和脑膜对PT呈免疫阳性;白色物质束也显示出与小静脉平行的细胞外PT的强表达。显微镜下，整个脑内有广泛的tau免疫反应神经元、星形细胞和变性神经突。在CTE血管周围缠结是最突出的。总的来说，CTE和对照组之间的染色强度存在显著差异（P<0.01），但CTE和TLE之间无显著差异（P=0.08）。pS199 tau分析显示CTE具有最高分子量的缠结相关tau，而癫痫脑含有低分子量tau。Tau沉积可能不是rTBI的特异性，因为TLE概括了CTE的大多数病理特征。
Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six post mortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE.