Department of Neurological Surgery, The Neurological Institute, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
Transl Stroke Res. 2012 Jul;3(Suppl 1):52-61. doi: 10.1007/s12975-012-0162-0. Epub 2012 Apr 12.
Intracerebral hemorrhage (ICH) is a devastating type of stroke with no effective therapies. Clinical advances in ICH treatment are limited by an incomplete understanding of the molecular mechanisms responsible for secondary injury and poor outcome. Increasing evidence suggests that cerebral edema is a major contributor to secondary injury and poor outcome in ICH. ICH activates specific signaling pathways that promote edema and damage neuronal tissue. By increasing our understanding of these pathways, we may be able to target them pharmaceutically to reduce edema in ICH patients. In this review, we focus on three major signaling pathways that promote edema after ICH: (1) the coagulation cascade and thrombin, (2) the inflammatory response and matrix metalloproteinases, and (3) the complement cascade and hemoglobin toxicity. We will describe the experimental evidence that confirms these pathways promote edema in ICH, discuss potential targets for new therapies, and comment on important directions for future research.
脑出血（ICH）是一种破坏性的中风类型，目前尚无有效的治疗方法。ICH 治疗的临床进展受到对导致继发性损伤和不良预后的分子机制理解不完整的限制。越来越多的证据表明，脑水肿是 ICH 继发性损伤和不良预后的主要原因。ICH 激活了特定的信号通路，促进了水肿和神经元组织的损伤。通过增加对这些途径的理解，我们也许能够通过药物靶向这些途径来减少 ICH 患者的水肿。在这篇综述中，我们重点关注促进 ICH 后水肿的三个主要信号通路：（1）凝血级联和凝血酶，（2）炎症反应和基质金属蛋白酶，以及（3）补体级联和血红蛋白毒性。我们将描述证实这些途径促进 ICH 水肿的实验证据，讨论新疗法的潜在靶点，并对未来研究的重要方向进行评论。
