ABSTRACT
Spontaneous intracerebral hemorrhage (ICH) is a catastrophic illness causing significant morbidity and mortality. Despite advances in surgical technique addressing primary brain injury caused by ICH, little progress has been made treating the subsequent inflammatory cascade. Pre-clinical studies have made advancements identifying components of neuroinflammation, including microglia, astrocytes, and T lymphocytes. After cerebral insult, inflammation is initially driven by the M1 microglia, secreting cytokines (e.g., interleukin-1β [IL-1β] and tumor necrosis factor-α) that are involved in the breakdown of the extracellular matrix, cellular integrity, and the blood brain barrier. Additionally, inflammatory factors recruit and induce differentiation of A1 reactive astrocytes and T helper 1 (Th1) cells, which contribute to the secretion of inflammatory cytokines, augmenting M1 polarization and potentiating inflammation. Within 7 days of ICH ictus, the M1 phenotype coverts to a M2 phenotype, key for hematoma removal, tissue healing, and overall resolution of inflammation. The secretion of anti-inflammatory cytokines (e.g., IL-4, IL-10) can drive Th2 cell differentiation. M2 polarization is maintained by the secretion of additional anti-inflammatory cytokines by the Th2 cells, suppressing M1 and Th1 phenotypes. Elucidating the timing and trigger of the anti-inflammatory phenotype may be integral in improving clinical outcomes. A challenge in current translational research is the absence of an equivalent disease animal model mirroring the patient population and comorbid pathophysiologic state. We review existing data and describe potential therapeutic targets around which we are creating a bench to bedside translational research model that better reflects the pathophysiology of ICH patients.
ABSTRACT
@#背景专家委员会制定的卒中康复指南应用于退伍军人健康管理部门及国防部卫生保健系统。方法根据以前发表的指南,委员会利用美国预防服务特别工作组制定的标准,评价了截至到2002年发表的文献。指南根据临床随机化实验、非对照性研究等证据提出建议(如缺乏确定的数据则根据专家组的建议)。结果Ⅰ级水平的建议包括:在多学科康复环境中或卒中单元中传递卒中治疗,通过NI HSS对卒中患者进行评价,早期启动康复治疗,对吞咽困难患者进行吞咽功能筛查,积极进行二级预防,预防深静脉血栓等。推荐应用标准化的评价工具制定适合每个患者的全面的治疗计划。强烈建议进行抗抑郁及情感波动方面的治疗。语言治疗师应评价患者的交流及认知障碍,并在需要时提供治疗。患者、家属及护理者是康复小组的重要成员,应当介入康复的全部疗程。这些建议在以下网站可查询:httP://stroke.ahajournals.org/cgi/content/full/36/9/e100。并附有每项建议的全文证据表。结论这些建议应平等地应用于所有临床环境中的所有卒中康复患者,而不是仅针对联邦医疗系统的临床问题或资源。