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生长因子和干细胞作为中风恢复的治疗方法。

Growth factors and stem cells as treatments for stroke recovery.

作者信息

Cairns Kevin, Finklestein Seth P

机构信息

Department of Physical Medicine and Rehabilitation, Harvard Medical School, 125 Nashua Street, Boston, Massachusetts 02114, USA.

出版信息

Phys Med Rehabil Clin N Am. 2003 Feb;14(1 Suppl):S135-42. doi: 10.1016/s1047-9651(02)00059-1.

Abstract

Both polypeptide growth factors and stem cell populations from bone marrow and umbilical cord blood hold promise as treatments to enhance neurologic recovery after stroke. Growth factors may exert their effects through stimulation of neural sprouting and enhancement of endogenous progenitor cell proliferation, migration, and differentiation in brain. Exogenous stem cells may exert their effects by acting as miniature "factories" for trophic substances in the poststroke brain. The combination of growth factors and stem cells may be more effective than either treatment alone. Stroke recovery represents a new and relatively untested target for stroke therapeutics. Whereas acute stroke treatments focus on agents that dissolve blot clots (thrombolytics) and antagonize cell death (neuroprotective agents), stroke recovery treatments are likely to enhance structural and functional reorganization (plasticity) of the damaged brain. Successful clinical trials of stroke recovery-promoting agents are likely to be quite different from trials testing acute stroke therapies. In particular, the time window of effective treatment to enhance stroke recovery is likely to be far longer than that for acute stroke treatments, perhaps days or weeks rather than minutes or hours after stroke. This longer time window means that time is available for careful screening and testing of potential subjects for stroke recovery trials, both in terms of size and location of cerebral infarcts and in type and severity of neurologic deficits. Detailed baseline information can be obtained for each patient against which eventual clinical outcome can be compared. Finally, separate and detailed outcome measures can be obtained in both the sensorimotor and cognitive neurologic spheres, because it is possible that these two kinds of function may recover differently or be differentially responsive to recovery-promoting treatments. Stroke recovery represents an important and underexplored opportunity for the development of new stroke treatments.

摘要

来自骨髓和脐带血的多肽生长因子及干细胞群体都有望成为促进中风后神经功能恢复的治疗手段。生长因子可能通过刺激神经发芽以及增强内源性祖细胞在脑内的增殖、迁移和分化来发挥作用。外源性干细胞可能通过充当中风后脑内营养物质的微型“工厂”来发挥作用。生长因子与干细胞联合使用可能比单独使用任何一种治疗方法都更有效。中风恢复是中风治疗学中一个新的且相对未经测试的靶点。急性中风治疗聚焦于溶解血栓的药物(溶栓剂)和拮抗细胞死亡的药物(神经保护剂),而中风恢复治疗则可能增强受损脑的结构和功能重组(可塑性)。促进中风恢复药物的成功临床试验可能与测试急性中风疗法的试验有很大不同。特别是,促进中风恢复的有效治疗时间窗可能远比急性中风治疗的时间窗长得多,可能是中风后的数天或数周,而不是数分钟或数小时。这个更长的时间窗意味着有时间对中风恢复试验的潜在受试者进行仔细筛选和测试,无论是从脑梗死的大小和位置,还是从神经功能缺损的类型和严重程度方面。可以为每位患者获取详细的基线信息,以便与最终的临床结果进行比较。最后,在感觉运动和认知神经领域都可以获得单独且详细的结果测量,因为这两种功能可能以不同方式恢复或对促进恢复的治疗有不同反应。中风恢复是开发新的中风治疗方法的一个重要且未被充分探索的机会。

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