NEURAL CHANGE FOLLOWING TRAUMATIC BRAIN INJURY

脑外伤后的神经变化

• 批准号: 3400443
• 负责人: John T Povlishock
• 金额: $ 19.97万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3400443
• 关键词: axon; brain injury; carbon; catecholamines; cats; electron microscopy; laboratory rat; microcapsule; microscopy; nervous system regeneration; neural degeneration; neuronal guidance; radionuclides; radiotracer; subarachnoid hemorrhage; subarachnoid space; trauma; vascular endothelium permeability

Traumatic brain injury (TBI) is a significant health care problem affecting over two million people a year. Although the pathobiology of all forms of TBI has not been completed characterized, most information suggests that, in the case of mild, moderate and severe TBI, axons are preferentially vulnerable to the forces of injury and that their injury explains much of the morbidity initially seen after TBI. with injury, axons are diffusely damaged throughout the brain with the result that damaged axons approximate undamaged axons of the same type. It is our premise that this situation allows the related undamaged fibers to sprout and reoccupy those synaptic sites deafferentated by the diffuse axonal injury, thereby contributing to the recovery seen with mild and some moderate injuries. This premise will be explored in well- controlled animal models of TBI known to produce diffuse axonal injury in specific brain sites. Anesthetized cats and rats will be subjected to moderate TBI and followed over an extended posttraumatic course. In the early postinjury period, antibodies to the 68kD neurofilament subunit will be employed to detect specific nuclear regions demonstrating axonal damage and therein the temporal course and pattern of perisomatic terminal loss a recovery will be followed. This will be accomplished by immunocytochemical approaches conducted at both the LM and EM level. These same approaches will be repeated in animals subjected to severe TBI to determine if the observed terminal loss and recovery replicates that seen with moderate TBI. The damaging consequences of a secondary sublethal ischemic insult on any recovery seen with moderate TBI will be assessed to gain further insight into the causes of less than optimal recovery seen in some moderate and virtually all severe TBIs. In concert with the above studies, the axonal events first associated with the genesis of TBI-induced change as well as those axonal changes occurring late in the postinjury course will be assessed through the use of antibodies to the 68kD subunit and anterogradely transported PHA-L respectively.

创伤性脑损伤 (TBI) 是一个重大的医疗保健问题 每年影响超过200万人。 虽然病理学 所有形式的 TBI 尚未完成表征，大多数信息 表明，在轻度、中度和重度 TBI 的情况下，轴突 优先容易受到伤害力的影响，并且他们的伤害 解释了 TBI 后最初出现的大部分发病情况。带着伤害， 整个大脑的轴突广泛受损，结果是 受损的轴突与相同类型的未受损的轴突近似。 这是我们的 前提是这种情况允许相关的未受损纤维 发芽并重新占据那些被弥漫性神经传导阻滞的突触位点 轴突损伤，从而有助于轻度和 一些中度伤害。 这个前提将得到很好的探索 已知可产生弥漫性轴突损伤的 TBI 对照动物模型 在特定的大脑部位。 麻醉的猫和老鼠将受到 中度 TBI，并进行长期的创伤后治疗。 在 损伤后早期，针对 68kD 神经丝的抗体 亚单位将用于检测特定的核区域 展示轴突损伤及其时间过程和模式 体周末期损失的恢复将随之而来。 这将是 通过在 LM 和 LM 进行的免疫细胞化学方法来完成 和电磁水平。 这些相同的方法将在动物身上重复 经受严重的 TBI 以确定观察到的终端损耗和 恢复情况与中度 TBI 的情况相同。 破坏性的 继发性亚致死性缺血性损伤对恢复的影响 将评估中度 TBI 所见，以进一步了解 在一些中等和几乎没有达到最佳恢复的原因 所有严重的 TBI。 与上述研究一致，轴突事件 首先与 TBI 引起的变化以及那些变化的发生有关 将评估损伤后过程后期发生的轴突变化 通过使用 68kD 亚基的抗体并顺行 分别运输PHA-L。