Department of Neurosurgery, Yale School of Medicine , New Haven, CT, USA.
Division of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School , Boston, MA, USA.
Expert Opin Investig Drugs. 2020 Oct;29(10):1099-1105. doi: 10.1080/13543784.2020.1813715. Epub 2020 Sep 20.
Research has advanced our understanding of the molecular and cellular mechanisms of cerebral edema and has propelled the development of novel antiedema therapeutics. Current evidence supports aberrant neuro-glial ion transport as a central mechanism that underlies pathological fluid accumulation after central nervous system injury.
Novel agents in clinical development show potential in altering the natural history and treatment of cerebral edema. Using the PubMed and Google Scholar databases, we review recent advances in our understanding of cerebral edema and describe agents under active investigation, their mechanism, and their application in recent and ongoing clinical trials.
Pharmacotherapies that target molecular mechanisms underlying the compensatory post-injury response of ion channels and transporters that lead to pathological alteration of osmotic gradients are the most promising therapeutic strategies. Repurposing of drugs such as glyburide that inhibit the aberrant upregulation of ion channels such as SUR1-TRPM4, and novel agents, such as ZT-1a, which reestablish physiological regulation of ion channels such as NKCC1/KCC, could be useful adjuvants to prevent and even reverse fluid accumulation in the brain parenchyma.
研究已经深入了解脑水肿的分子和细胞机制，并推动了新型抗水肿治疗方法的发展。目前的证据支持异常的神经胶质离子转运作为中枢神经系统损伤后病理性液体积累的核心机制。
临床开发中的新型药物具有改变脑水肿自然病程和治疗的潜力。我们使用 PubMed 和 Google Scholar 数据库，回顾了我们对脑水肿的理解的最新进展，并描述了正在积极研究的药物、它们的作用机制以及它们在最近和正在进行的临床试验中的应用。
针对导致渗透性梯度病理性改变的离子通道和转运体补偿性损伤后反应的分子机制的药物治疗是最有前途的治疗策略。重新利用药物（如抑制 SUR1-TRPM4 等异常上调的离子通道的格列本脲）和新型药物（如重新建立 NKCC1/KCC 等离子通道生理调节的 ZT-1a）可能是预防甚至逆转脑实质液体积累的有用辅助手段。
