Neurobehavioral, cellular, and molecular consequences of single and multiple mild blast exposure
Neurobehavioral, cellular, and molecular consequences of single and multiple mild blast exposure
复制标题
DOI：
10.1002/elps.201200319
复制
发表时间：
2012-12-01
期刊：
影响因子：
2.9
通讯作者：
Agoston, Denes
中科院分区：
文献类型：
--
作者：
Kamnaksh, Alaa;Kwon, Sook-Kyung;Agoston, Denes
由暴露于单次或多次爆炸超压引起的轻度创伤性脑损伤是一个主要问题，因为其病理复杂性和与创伤后应激障碍的神经行为相似性。在这项研究中，我们将大鼠暴露于单个或多个（总共5个;连续几天给药）轻度爆炸，在损伤后1天和16天评估其行为，并在早期（2小时）和晚期（22天）终止时间点进行脑和血浆的组织学和蛋白质分析。损伤后一天，多发伤（MI）大鼠表现出最少的一般运动和最抑郁和焦虑相关的行为之间的实验组，有没有这样的差异在16天。然而，在后来的时间点，两个受伤组都显示出选定蛋白质生物标志物水平升高。组织学显示，早在损伤后2小时，两个损伤组的背侧和腹侧海马（DHC和VHC）中TUNEL+（末端脱氧转移酶介导的dUTP缺口末端标记）阳性细胞的数量显著增加。在第22天，增加仅限于MI动物的VHC。我们的研究结果表明，暴露于轻度冲击波超压触发早期海马细胞死亡以及神经元，神经胶质细胞和血管损伤，这可能有助于显着的，虽然短暂的增加抑郁和焦虑相关的行为。然而，在MI大鼠中观察到的病理变化的严重程度未能支持重复损伤的假设累积效应。我们推断，在这个冲击波频率，一个潜在的条件反射现象抵消，并减少了随后的损害程度在MI大鼠。
Mild traumatic brain injury, caused by the exposure to single or repeated blast overpressure, is a principal concern due to its pathological complexity and neurobehavioral similarities with posttraumatic stress disorder. In this study, we exposed rats to a single or multiple (five total; administered on consecutive days) mild blasts, assessed their behavior at 1 and 16 days postinjury) and performed histological and protein analyses of brains and plasma at an early (2 h) and a late (22 days) termination time point. One day postinjury, multiple-injured (MI) rats showed the least general locomotion and the most depression- and anxiety-related behaviors among the experimental groups; there were no such differences at 16 days. However, at the later time point, both injured groups displayed elevated levels of select protein biomarkers. Histology showed significantly increased numbers of TUNEL+ (terminal-deoxy-transferase-mediated dUTP nick-end labeling)-positive cells in the dorsal and ventral hippocampus (DHC and VHC) of both injured groups as early as 2 h after injury. At 22 days, the increase was limited to the VHC of MI animals. Our findings suggest that the exposure to mild blast overpressure triggers early hippocampal cell death as well as neuronal, glial, and vascular damage that likely contribute to significant, albeit transient increases in depression- and anxiety-related behaviors. However, the severity of the observed pathological changes in MI rats failed to support the hypothesized cumulative effect of repeated injury. We infer that at this blast frequency, a potential conditioning phenomenon counteracts with and reduces the extent of subsequent damage in MI rats.