中风患者的福音!联合治疗能够恢复中风患者的认知能力且延长治疗窗口期

2020-06-09 转化医学网 转化医学网

再灌注治疗是中风治疗的金标准,有助于在血栓引起的中风后恢复血流量,防止脑组织损伤。

再灌注治疗是中风治疗的金标准,有助于在血栓引起的中风后恢复血流量,防止脑组织损伤。然而,只有大约10%的中风患者符合条件,部分原因是再灌注治疗的治疗窗口狭窄。

  南卡罗来纳州医科大学(Medical University of South Carolina)最近的一项研究表明,如果使用一种阻断免疫反应的特殊化合物,这种疗法对运动和认知恢复既安全又有效。5月13日出版在《神经科学杂志》(Journal of Neuroscience)封面文章报道了该研究小组的临床前发现,减少大脑的免疫反应可能是改善认知恢复的一种策略。它还可以扩大治疗窗口,让中风专家帮助更多的中风患者。

  马斯克微生物和免疫学系临时主席、文章高级作者斯蒂芬·汤姆林森(Stephen Tomlinson)博士表示,“通过再灌注治疗,我们正在恢复血流,这是挽救组织所必需的,但免疫系统正在发生炎症反应,这不是再灌注的靶点。”这可以解释为什么,尽管机械再灌注在将血液回流到大脑方面有90%的成功率,但只有大约40%的接受治疗的患者在三个月内恢复了足够的运动和推理能力,能够独立处理日常需要。即使那些确实恢复了运动功能的人,几个月后仍会面临认知挑战。
  在MUSC完成了研究生学业,现在是埃默里大学医学院神经外科的住院医师、该研究的主要作者阿里·阿拉维赫(Ali Alawieh)博士表示,“我在随访中见过几乎没有任何运动障碍的患者,但他们在日常生活中确实在记忆、行为后果和语言方面存在障碍。”
  一个称为补体蛋白的特殊免疫蛋白家族有助于在受损区域引导和促进这种免疫反应。
 在2018年发表在《科学转化医学》(Science Translation Medicine)上的一篇文章中,汤姆林森和阿拉维表示,这些补体蛋白标记了死亡组织和受压迫的脑细胞,以便清除它们。
  受压迫的脑细胞还没有死亡,只是由于缺氧和能量不足而受损。由于中风治疗的目标是尽可能多地保存脑组织以减轻整体损伤,这是一个令人担忧的结果,因为这意味着可挽救的组织被免疫系统破坏了。
  因此,汤姆林森和他的团队开发了一种补体蛋白阻滞剂,名为B4Crry,只在中风损伤部位起作用。在临床前中风模型中,这种复合物使补体蛋白对应激脑细胞的信号失去作用,从而保存应激组织并减少整体脑损伤。
  在目前的研究中,汤姆林森和阿拉维假设,再灌注疗法和B4Crry的联合治疗比单独再灌注治疗更能显著改善中风恢复。最为重要的是,他们假设这种联合治疗可以改善认知恢复。
  正如汤姆林森的研究小组所预期的那样,在临床前中风模型中,单独的再灌注疗法确实能改善协调运动的恢复,例如行走。随着B4Crry的加入治疗,协调运动改善得更快,中风3天后就有了很好的恢复。在学习和记忆的改善甚至比运动功能方面的改善更大。
  对于脑卒中后的学习和记忆恢复,单独再灌注治疗等同于完全不治疗。然而,当B4Crry被添加到他们的治疗中时,小鼠的认知恢复能力得到了极大地改善,在学习和记忆任务中的错误减少了三倍。
  汤姆林森的研究小组进一步探讨了为什么B4Crry的加入,以及随后大脑免疫反应的降低,对认知恢复有如此大的帮助。他们发现,中风后,被称为小胶质细胞的脑免疫细胞开始吞噬应激脑细胞之间的连接。免疫系统补体蛋白标记这些连接以便破坏,因为它们显示了应激细胞的信号。如果没有这些连接,脑细胞就不能有效地交流,整个大脑功能就会下降。B4Crry从补体蛋白中隐藏了细胞的应激信号,从而保存了神经元之间的连接。保持连接性可以改善脑卒中后的学习和记忆功能。
  补体抑制剂如B4Crry也可以帮助中风专家克服再灌注治疗的最大障碍:治疗窗口短。汤姆林森的研究小组表明,在血栓清除后,即使在中风后6小时内进行治疗,在再灌注疗法中加入B4Crry仍可以降低出血或过多出血的可能性。这些结果表明,补体抑制不再仅可以使灌注治疗更安全,而且可以扩大其治疗范围,使其可用于更多的脑卒中患者。
  阿拉维赫解释说:“我对补体抑制在临床上的应用感到兴奋,我们下一步要做的就是在临床前研究中观察补体抑制剂如何与老年、吸烟和糖尿病等共病协同作用的。总体而言,这些信息将有助于我们设计用于人体的最佳临床试验。”
  汤姆林森表示:“我们已经证明,我们可以在创伤性脑损伤后两个月后使用补体抑制剂,并看到了认知恢复的改善。这让我感到非常兴奋。这意味着,在中风发生数月后,补体抑制剂可能仍对包括中风在内的脑损伤后的认知恢复有益。”
  导言:

【1】https://medicalxpress.com/news/2020-06-inflammation-boosts-cognitive-recovery-treatment.html

【2】https://www.jneurosci.org/content/40/20/4042

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    2021-02-15 海1991

    学习了

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    2020-12-19 燃烧的火柴

    0

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    2020-06-09 guging

    中风是俗称,应该称为缺血性卒中吧

    0

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