中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (3): 341-350.doi: 10.4103/1673-5374.202915

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

脑保护机制和治疗性低温治疗卒中的转化潜力

  

  • 收稿日期:2017-02-18 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    本文由美国心脏协会(AHA)博士后奖学金15POST25680013(JHL)、国家卫生研究院基金NS085568(SPY)和弗吉尼亚州绩效拨款RX000666(SPY)共同赞助

Neuroprotective mechanisms and translational potential of therapeutic hypothermia in the treatment of ischemic stroke

Jin Hwan Lee, James Zhang, Shan Ping Yu   

  • Received:2017-02-18 Online:2017-03-15 Published:2017-03-15
  • Contact: Shan Ping Yu, M.D., Ph.D., spyu@emory.edu.
  • Supported by:

    This paper was supported by an American Heart Association (AHA) Postdoctoral Fellowship 15POST25680013 (JHL), NIH grants NS085568 (SPY), and a VA Merit grant RX000666 (SPY).

摘要:

在几十年的广泛研究之后,脑卒中仍然是残疾和死亡的主要原因,并且目前对急性脑卒中的有效治疗非常有限。组织纤溶酶原激活剂是迄今为止FDA唯一批准用于对缺血性脑卒中患者进行溶栓治疗的药物,然而由于狭窄的治疗窗口(<4.5小时后),其仅能使少于4-5%的脑卒中患者获益,并伴有出血性变化的高风险。来自基础和临床研究的新证据表明,治疗性低温是对不同类型脑卒中的患者有前途的治疗方法。此外,在使用药理学诱导的低温(PIH)动物模型已经成功增强了低温疗法临床翻译的信心。
本文提供了包括最近开发的PIH治疗的治疗性低温机制和保护作用的总体情况。预期安全有效的降温疗法对于患有脑卒中和其它中枢神经系统损伤患者的临床治疗具有高的翻译潜力。

ORCID:0000-0003-1335-1398(Shan Ping Yu)

Abstract:

Stroke is a leading cause of disability and death, yet effective treatments for acute stroke has been very limited. Thus far, tissue plasminogen activator has been the only FDA-approved drug for thrombolytic treatment of ischemic stroke patients, yet its application is only applicable to less than 4–5% of stroke patients due to the narrow therapeutic window (< 4.5 hours after the onset of stroke) and the high risk of hemorrhagic transformation. Emerging evidence from basic and clinical studies has shown that therapeutic hypothermia, also known as targeted temperature management, can be a promising therapy for patients with different types of stroke. Moreover, the success in animal models using pharmacologically induced hypothermia (PIH) has gained increasing momentum for clinical translation of hypothermic therapy. This review provides an updated overview of the mechanisms and protective effects of therapeutic hypothermia, as well as the recent development and findings behind PIH treatment. It is expected that a safe and effective hypothermic therapy has a high translational potential for clinical treatment of patients with stroke and other CNS injuries.

Key words: stroke, therapeutic hypothermia, drug-induced hypothermia, ischemia, cell death, inflammation