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Abstract：
OBJECTIVE: The purposes of this narrative review are to (1) summarize a contemporary view of cerebral edema pathophysiology, (2) present a synopsis of current management strategies in the context of their historical roots (many of which date back multiple centuries), and (3) discuss contributions of key molecular pathways to overlapping edema endophenotypes. This may facilitate identification of important therapeutic targets.
RESULTS: Cerebral edema and resultant intracranial hypertension are major contributors to morbidity and mortality following traumatic brain injury. Although Starling forces are physical drivers of edema based on differences in intravascular vs extracellular hydrostatic and oncotic pressures, the molecular pathophysiology underlying cerebral edema is complex and remains incompletely understood. Current management protocols are guided by intracranial pressure measurements, an imperfect proxy for cerebral edema. These include decompressive craniectomy, external ventricular drainage, hyperosmolar therapy, hypothermia, and sedation. Results of contemporary clinical trials assessing these treatments are summarized, with an emphasis on the gap between intermediate measures of edema and meaningful clinical outcomes. This is followed by a brief statement summarizing the most recent guidelines from the Brain Trauma Foundation (4th edition). While many molecular mechanisms and networks contributing to cerebral edema after TBI are still being elucidated, we highlight some promising molecular mechanism-based targets based on recent research including SUR1-TRPM4, NKCC1, AQP4, and AVP1.
CONCLUSIONS: This review outlines the origins of our understanding of cerebral edema, chronicles the history behind many current treatment approaches, and discusses promising molecular mechanism-based targeted treatments.
RESULTS: Cerebral edema and resultant intracranial hypertension are major contributors to morbidity and mortality following traumatic brain injury. Although Starling forces are physical drivers of edema based on differences in intravascular vs extracellular hydrostatic and oncotic pressures, the molecular pathophysiology underlying cerebral edema is complex and remains incompletely understood. Current management protocols are guided by intracranial pressure measurements, an imperfect proxy for cerebral edema. These include decompressive craniectomy, external ventricular drainage, hyperosmolar therapy, hypothermia, and sedation. Results of contemporary clinical trials assessing these treatments are summarized, with an emphasis on the gap between intermediate measures of edema and meaningful clinical outcomes. This is followed by a brief statement summarizing the most recent guidelines from the Brain Trauma Foundation (4th edition). While many molecular mechanisms and networks contributing to cerebral edema after TBI are still being elucidated, we highlight some promising molecular mechanism-based targets based on recent research including SUR1-TRPM4, NKCC1, AQP4, and AVP1.
CONCLUSIONS: This review outlines the origins of our understanding of cerebral edema, chronicles the history behind many current treatment approaches, and discusses promising molecular mechanism-based targeted treatments.
摘要：
目的：这篇叙述性综述的目的是（1）总结脑水肿病理生理学的当代观点，（2）在其历史根源的背景下提出当前管理策略的概要（其中许多可以追溯到多个世纪），（3）讨论关键分子途径对重叠水肿表型的贡献。这可以促进重要治疗靶标的鉴定。
结果：脑水肿和由此产生的颅内高压是创伤性脑损伤后发病率和死亡率的主要原因。尽管Starling力是基于血管内与细胞外静水压和致癌压力差异的水肿的物理驱动因素，脑水肿背后的分子病理生理学是复杂的，仍然不完全了解。目前的管理方案是由颅内压测量指导的，脑水肿的不完美代表.这些包括去骨瓣减压术,脑室外引流,高渗疗法,体温过低,和镇静。总结了评估这些治疗方法的当代临床试验结果，强调水肿的中间指标和有意义的临床结果之间的差距。接下来是简短的声明，总结了脑外伤基金会（第4版）的最新指南。虽然导致TBI后脑水肿的许多分子机制和网络仍在阐明，基于最近的研究,我们重点介绍了一些有前景的基于分子机制的靶标,包括SUR1-TRPM4,NKCC1,AQP4和AVP1.
结论：这篇综述概述了我们对脑水肿的理解的起源，记录了许多当前治疗方法背后的历史，并讨论了有希望的基于分子机制的靶向治疗。
结果：脑水肿和由此产生的颅内高压是创伤性脑损伤后发病率和死亡率的主要原因。尽管Starling力是基于血管内与细胞外静水压和致癌压力差异的水肿的物理驱动因素，脑水肿背后的分子病理生理学是复杂的，仍然不完全了解。目前的管理方案是由颅内压测量指导的，脑水肿的不完美代表.这些包括去骨瓣减压术,脑室外引流,高渗疗法,体温过低,和镇静。总结了评估这些治疗方法的当代临床试验结果，强调水肿的中间指标和有意义的临床结果之间的差距。接下来是简短的声明，总结了脑外伤基金会（第4版）的最新指南。虽然导致TBI后脑水肿的许多分子机制和网络仍在阐明，基于最近的研究,我们重点介绍了一些有前景的基于分子机制的靶标,包括SUR1-TRPM4,NKCC1,AQP4和AVP1.
结论：这篇综述概述了我们对脑水肿的理解的起源，记录了许多当前治疗方法背后的历史，并讨论了有希望的基于分子机制的靶向治疗。
