Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Adelaide 5005, Australia.
Brain Sci. 2013 Jan 30;3(1):123-42. doi: 10.3390/brainsci3010123.
Stroke is a leading cause of death, disability and dementia worldwide. Despite extensive pre-clinical investigation, few therapeutic treatment options are available to patients, meaning that death, severe disability and the requirement for long-term rehabilitation are common outcomes. Cell loss and tissue injury following stroke occurs through a number of diverse secondary injury pathways, whose delayed nature provides an opportunity for pharmacological intervention. Amongst these secondary injury factors, increased blood-brain barrier permeability and cerebral oedema are well-documented complications of cerebral ischaemia, whose severity has been shown to be associated with final outcome. Whilst the mechanisms of increased blood-brain barrier permeability and cerebral oedema are largely unknown, recent evidence suggests that the neuropeptide substance P (SP) plays a central role. The aim of this review is to examine the role of SP in ischaemic stroke and report on the potential utility of NK1 tachykinin receptor antagonists as therapeutic agents.
中风是全球范围内导致死亡、残疾和痴呆的主要原因。尽管进行了广泛的临床前研究,但可供患者选择的治疗方法很少,这意味着死亡、严重残疾和长期康复的需求是常见的结果。中风后细胞死亡和组织损伤是通过多种不同的继发损伤途径发生的,其延迟性质为药物干预提供了机会。在这些继发损伤因素中,血脑屏障通透性增加和脑水肿是脑缺血的公认并发症,其严重程度已被证明与最终结果有关。虽然增加血脑屏障通透性和脑水肿的机制在很大程度上尚不清楚,但最近的证据表明神经肽物质 P(SP)起着核心作用。本综述的目的是检查 SP 在缺血性中风中的作用,并报告 NK1 速激肽受体拮抗剂作为治疗剂的潜在效用。