时间能治愈所有创伤吗？实验性弥漫性创伤性脑损伤会导致丘脑持续存在组织病理学变化。
Does time heal all wounds? Experimental diffuse traumatic brain injury results in persisting histopathology in the thalamus.
作者信息
Thomas Theresa Currier, Ogle Sarah B, Rumney Benjamin M, May Hazel G, Adelson P David, Lifshitz Jonathan
机构信息
Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA; Phoenix VA Health Care System, Phoenix, AZ, USA.
Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA; Phoenix Integrated Surgical Residency, Banner University Medical Center, Phoenix, AZ, USA; Department of Surgery, Banner University Medical Center, Phoenix, AZ, USA.
出版信息
Behav Brain Res. 2018 Mar 15;340:137-146. doi: 10.1016/j.bbr.2016.12.038. Epub 2016 Dec 29.
BACKGROUND
Thalamic dysfunction has been implicated in overall chronic neurological dysfunction after traumatic brain injury (TBI), however little is known about the underlying histopathology. In experimental diffuse TBI (dTBI), we hypothesize that persisting histopathological changes in the ventral posteromedial (VPM) nucleus of the thalamus is indicative of progressive circuit reorganization. Since circuit reorganization in the VPM impacts the whisker sensory system, the histopathology could explain the development of hypersensitivity to whisker stimulation by 28days post-injury; similar to light and sound hypersensitivity in human TBI survivors.
METHODS
Adult, male Sprague-Dawley rats underwent craniotomy and midline fluid percussion injury (FPI) (moderate severity; 1.8-2.0atm) or sham surgery. At 1d, 7d, and 28days post-FPI (d FPI) separate experiments confirmed the cytoarchitecture (Giemsa stain) and evaluated neuropathology (silver stain), activated astrocytes (GFAP), neuron morphology (Golgi stain) and microglial morphology (Iba-1) in the VPM.
RESULTS
Cytoarchitecture was unchanged throughout the time course, similar to previously published data; however, neuropathology and astrocyte activation were significantly increased at 7d and 28d and activated microglia were present at all time points. Neuron morphology was dynamic over the time course with decreased dendritic complexity (fewer branch points; decreased length of processes) at 7d FPI and return to sham values by 28d FPI.
CONCLUSIONS
These data indicate that dTBI results in persisting thalamic histopathology out to a chronic time point. While these changes can be indicative of either adaptive (recovery) or maladaptive (neurological dysfunction) circuit reorganization, they also provide a potential mechanism by which maladaptive circuit reorganization could contribute to the development of chronic neurological dysfunction. Understanding the processes that mediate circuit reorganization is critical to the development of future therapies for TBI patients.
背景
丘脑功能障碍与创伤性脑损伤（TBI）后的整体慢性神经功能障碍有关，然而其潜在的组织病理学情况却知之甚少。在实验性弥漫性脑损伤（dTBI）中，我们假设丘脑腹后内侧（VPM）核持续存在的组织病理学变化表明神经回路在进行性重组。由于VPM中的神经回路重组会影响触须感觉系统，这种组织病理学变化可以解释在损伤后28天时对触须刺激过敏的发生；类似于人类TBI幸存者对光和声的过敏。
方法
成年雄性Sprague-Dawley大鼠接受开颅手术和中线流体冲击伤（FPI）（中度严重程度；1.8 - 2.0个大气压）或假手术。在FPI后1天、7天和28天（d FPI）进行单独实验，确认细胞结构（吉姆萨染色）并评估神经病理学（银染色）、活化星形胶质细胞（GFAP）、神经元形态（高尔基染色）和VPM中的小胶质细胞形态（Iba-1）。
结果
在整个时间进程中细胞结构没有变化，与先前发表的数据相似；然而，神经病理学和星形胶质细胞活化在7天和28天时显著增加，并且在所有时间点都存在活化的小胶质细胞。神经元形态在整个时间进程中是动态变化的，在FPI后7天时树突复杂性降低（分支点减少；突起长度缩短），到FPI后28天时恢复到假手术组的值。
结论
这些数据表明dTBI会导致丘脑组织病理学变化持续到慢性时间点。虽然这些变化可能表明适应性（恢复）或适应不良（神经功能障碍）的神经回路重组，但它们也提供了一种潜在机制，通过这种机制适应不良的神经回路重组可能导致慢性神经功能障碍的发生。了解介导神经回路重组的过程对于开发未来治疗TBI患者的疗法至关重要。
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