Physiology.
Surgery, Faculty of Medicine, University of Toronto.
Acta Pharmacol Sin. 2018 May;39(5):695-712. doi: 10.1038/aps.2018.23. Epub 2018 Apr 19.
Stroke can lead to long-term neurological deficits. Adult neurogenesis, the continuous generation of newborn neurons in distinct regions of the brain throughout life, has been considered as one of the appoaches to restore the neurological function following ischemic stroke. However, ischemia-induced spontaneous neurogenesis is not suffcient, thus cell-based therapy, including infusing exogenous stem cells or stimulating endogenous stem cells to help repair of injured brain, has been studied in numerous animal experiments and some pilot clinical trials. While the effects of cell-based therapy on neurological function during recovery remains unproven in randomized controlled trials, pharmacological agents have been administrated to assist the cell-based therapy. In this review, we summarized the limitations of ischemia-induced neurogenesis and stem-cell transplantation, as well as the potential proneuroregenerative effects of drugs that may enhance efficacy of cell-based therapies. Specifically, we discussed drugs that enhance proliferation, migration, differentiation, survival and function connectivity of newborn neurons, which may restore neurobehavioral function and improve outcomes in stroke patients.
中风可导致长期神经功能缺损。成人神经发生,即一生中大脑特定区域持续产生新生神经元,被认为是恢复缺血性中风后神经功能的一种方法。然而,缺血诱导的自发神经发生是不足够的,因此细胞疗法,包括输注外源性干细胞或刺激内源性干细胞以帮助受损大脑的修复,已在许多动物实验和一些初步临床试验中进行了研究。虽然细胞疗法对随机对照试验中恢复期间神经功能的影响仍未得到证实,但已给予了药理学药物以辅助细胞疗法。在这篇综述中,我们总结了缺血诱导的神经发生和干细胞移植的局限性,以及可能增强细胞疗法疗效的促神经再生药物的潜在作用。具体而言,我们讨论了增强新生神经元增殖、迁移、分化、存活和功能连接的药物,这些药物可能恢复神经行为功能并改善中风患者的预后。