Moderately elevated intracranial pressure after diffuse traumatic brain injury is associated with exacerbated neuronal pathology and behavioral morbidity in the rat
Moderately elevated intracranial pressure after diffuse traumatic brain injury is associated with exacerbated neuronal pathology and behavioral morbidity in the rat
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DOI：
10.1038/jcbfm.2014.122
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发表时间：
2014-10-01
影响因子：
6.3
通讯作者：
Povlishock, John T.
中科院分区：
文献类型：
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作者：
Lafrenaye, Audrey D.;Krahe, Thomas E.;Povlishock, John T.
外伤性脑损伤（TBI）引起的颅内压升高与随后的人类发病率/死亡率相关。这种关系被认为主要依赖于这样一种认识，即ICP的极度升高要么表明血肿/挫伤能够导致疝，要么改变脑灌注压（CPP），从而导致全身缺血。然而，没有血肿/挫伤的亚缺血水平升高的ICP是否会增加发病率/死亡率仍然未知。为了解决这一知识缺口，我们利用了一个中度弥漫性脑损伤大鼠模型，随后进行了脑室内ICP监测或手动将ICP升高至20 mm Hg，其中CPP高于缺血水平。评估脑外伤后颅内压升高对急性和慢性组织病理学的影响，以及对行为发病率的影响。颅脑损伤后颅内压升高导致急性神经元膜摄动增加，也与损伤后4周神经元密度降低有关。体感超敏反应因ICP升高而加重，并与观察到的神经元损失相关。总之，本研究表明，与ICP升高相关的发病率和神经元损伤/死亡增加可以在没有同时发生的全局缺血的情况下发生。因此，了解与亚缺血水平升高的颅内压相关的病理可以为TBI患者的治疗和管理提供更好的治疗策略。
Traumatic brain injury (TBI)-induced elevated intracranial pressure (ICP) is correlated with ensuing morbidity/mortality in humans. This relationship is assumed to rely mostly on the recognition that extremely elevated ICP either indicates hematoma/contusions capable of precipitating herniation or alters cerebral perfusion pressure (CPP), which precipitates global ischemia. However, whether subischemic levels of elevated ICP without hematoma/contusion contribute to increased morbidity/mortality remains unknown. To address this knowledge gap, we utilized a model of moderate diffuse TBI in rats followed by either intraventricular ICP monitoring or manual ICP elevation to 20 mm Hg, in which CPP was above ischemic levels. The effects of ICP elevation after TBI on acute and chronic histopathology, as well as on behavioral morbidity, were evaluated. ICP elevation after TBI resulted in increased acute neuronal membrane perturbation and was also associated with reduced neuronal density at 4 weeks after injury. Somatosensory hypersensitivity was exacerbated by ICP elevation and was correlated to the observed neuronal loss. In conclusion, this study indicates that morbidity and increased neuronal damage/death associated with elevated ICP can occur without concurrent global ischemia. Therefore, understanding the pathologies associated with subischemic levels of elevated ICP could lead to the development of better therapeutic strategies for the treatment and management of TBI patients.