Inflammation and white matter degeneration persist for years after a single traumatic brain injury
Inflammation and white matter degeneration persist for years after a single traumatic brain injury
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DOI：
10.1093/brain/aws322
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发表时间：
2013-01-01
期刊：
影响因子：
14.5
通讯作者：
Stewart, William
中科院分区：
文献类型：
--
作者：
Johnson, Victoria E.;Stewart, Janice E.;Stewart, William
单一的创伤性脑损伤与痴呆症风险的增加有关，并且在受伤后存活一年或更长时间的患者中，部分患者会出现标志性阿尔茨海默病样病理。然而，创伤性脑损伤和神经退行性疾病的病理过程仍然知之甚少。越来越多的证据支持神经炎症在阿尔茨海默病发展中的作用。相反，我们对脑损伤的神经炎症反应知之甚少，特别是其时间动力学和在神经退行性变中的任何潜在作用。从格拉斯哥创伤性脑损伤档案中选择创伤性脑损伤患者（n = 52）和年龄匹配的未受伤对照受试者（n = 44），创伤性脑损伤患者的存活时间范围为10 h至47年。从这些，胼胝体和相邻的旁枕叶皮质的切片检查小胶质细胞密度和形态，以及白色物质病理学和完整性的指数。创伤性脑损伤患者的生存期为103个月，经常出现广泛、密集的反应性小胶质细胞（CR 3/43和/或CD 68免疫反应性），这在对照受试者或急性损伤病例中未见。特别值得注意的是，这些反应性小胶质细胞存在于28%的创伤后生存期> 1年和长达18年的病例中。在显示这种炎症病理学的病例中，还可以观察到持续的白色物质降解的证据。此外，胼胝体厚度减少25%，损伤后存活> 1年。这些数据提供了惊人的证据，表明人类在单一创伤性脑损伤后多年持续存在炎症和持续的白色变性。未来的研究，以确定是否发生炎症反应，或相反，促进白色物质变性将是重要的。这些发现可能为研究神经退行性疾病提供了相似之处，创伤性脑损伤患者可作为纵向调查的模型，特别是为了确定潜在的治疗干预措施。
A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer's disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer's disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of epsilon 3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of > 1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival > 1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions.