Rodriguez-Paez Alejandra C, Brunschwig J P, Bramlett Helen M
Neurotrauma Research Center, The Miami Project to Cure Paralysis, Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Acta Neuropathol. 2005 Jun;109(6):603-16. doi: 10.1007/s00401-005-1010-z. Epub 2005 May 5.
The presence of progressive white matter atrophy following traumatic brain injury (TBI) has been reported in humans as well as in animal models. However, a quantitative analysis of progressive alterations in myelinated axons and other cellular responses to trauma has not been conducted. This study examined quantitative differences in myelinated axons from several white and gray matter structures between non-traumatized and traumatized areas at several time points up to 1 year. We hypothesize that axonal numbers decrease over time within the structures analyzed, based on our previous work demonstrating shrinkage of tissue in these vulnerable areas. Intubated, anesthetized male Sprague-Dawley rats were subjected to moderate (1.8-2.2 atm) parasagittal fluid-percussion brain injury, and perfused at various intervals after surgery. Sections from the fimbria, external capsule, thalamus and cerebral cortex from the ipsilateral hemisphere of traumatized and sham-operated animals were prepared and. estimated total numbers of myelinated axons were determined by systematic random sampling. Electron micrographs were obtained for ultrastructural analysis. A significant (P<0.05) reduction in the number of myelinated axons in the traumatized hemisphere compared to control in all structures was observed. In addition, thalamic and cortical axonal counts decreased significantly (P<0.05) over time. Swollen axons and macrophage/microglia infiltration were present as late as 6 months post-TBI in various structures. This study is the first to describe quantitatively chronic axonal changes in vulnerable brains regions after injury. Based on these data, a time-dependent decrease in the number of myelinated axons is seen to occur in vulnerable gray matter regions including the cerebral cortex and thalamus along with distinct morphological changes within white matter tracts after TBI. Although this progressive axonal response to TBI may include Wallerian degeneration, other potential mechanisms underlying this progressive pathological response within the white matter are discussed.
在人类以及动物模型中均已报道创伤性脑损伤（TBI）后存在进行性白质萎缩。然而，尚未对有髓轴突的进行性改变以及其他细胞对创伤的反应进行定量分析。本研究在长达1年的多个时间点，检查了非创伤区域和创伤区域之间几个白质和灰质结构中有髓轴突的定量差异。基于我们之前证明这些易损区域组织萎缩的研究工作，我们假设在所分析的结构中轴突数量会随时间减少。对插管麻醉的雄性Sprague-Dawley大鼠施加中度（1.8 - 2.2个大气压）矢状旁流体冲击性脑损伤，并在术后不同时间间隔进行灌注。制备创伤动物和假手术动物同侧半球的海马伞、外囊、丘脑和大脑皮质的切片，并通过系统随机抽样确定有髓轴突的估计总数。获取电子显微镜照片用于超微结构分析。观察到与对照组相比，所有结构中创伤半球的有髓轴突数量均显著减少（P<0.05）。此外，丘脑和皮质的轴突计数随时间显著减少（P<0.05）。在TBI后长达6个月时，不同结构中仍存在轴突肿胀以及巨噬细胞/小胶质细胞浸润。本研究首次定量描述了损伤后易损脑区的慢性轴突变化。基于这些数据，TBI后在包括大脑皮质和丘脑在内的易损灰质区域，可见有髓轴突数量随时间减少，同时白质束内出现明显的形态学变化。尽管这种对TBI的进行性轴突反应可能包括沃勒变性，但也讨论了白质内这种进行性病理反应的其他潜在机制。
