Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan.
Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Helsinki, Finland.
Sci Rep. 2017 Jul 3;7(1):4512. doi: 10.1038/s41598-017-04048-2.
The purpose of this study was to examine the neurorestorative effect of delayed 9 cis retinoic acid (9cRA) treatment for stroke. Adult male rats received a 90-min right distal middle cerebral artery occlusion (dMCAo). Animals were separated into two groups with similar infarction sizes, based on magnetic resonance imaging on day 2 after dMCAo. 9cRA or vehicle was given via an intranasal route daily starting from day 3. Stroke rats receiving 9cRA post-treatment showed an increase in brain 9cRA levels and greater recovery in motor function. 9cRA enhanced the proliferation of bromodeoxyuridine (+) cells in the subventricular zone (SVZ) and lesioned cortex in the stroke brain. Using subventricular neurosphere and matrigel cultures, we demonstrated that proliferation and migration of SVZ neuroprogenitor cells were enhanced by 9cRA. Our data support a delayed and non-invasive drug therapy for stroke. Intranasal 9cRA can facilitate the functional recovery and endogenous repair in the ischemic brain.
本研究旨在探讨延迟给予 9-顺式视黄酸(9cRA)治疗对脑卒中的神经修复作用。成年雄性大鼠接受 90 分钟右侧大脑中动脉远端闭塞(dMCAo)。根据 dMCAo 后第 2 天的磁共振成像,将动物分为两组,两组梗死大小相似。从第 3 天开始,通过鼻腔途径每日给予 9cRA 或载体。脑卒中大鼠接受 9cRA 后治疗显示大脑中 9cRA 水平增加,运动功能恢复更好。9cRA 增强了脑卒中大脑侧脑室下区(SVZ)和损伤皮质中溴脱氧尿苷(+)细胞的增殖。通过 SVZ 神经球和基质胶培养,我们证明 9cRA 增强了 SVZ 神经祖细胞的增殖和迁移。我们的数据支持对脑卒中进行延迟和非侵入性的药物治疗。鼻腔内给予 9cRA 可促进缺血性大脑的功能恢复和内源性修复。