Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, S-22184 Lund, Sweden.
Stroke. 2012 Feb;43(2):507-13. doi: 10.1161/STROKEAHA.111.638767. Epub 2011 Nov 17.
Delayed treatment of patients with stroke with levodopa/benserazide contributes to enhanced functional recovery, but the mechanisms involved are poorly understood. The present study was designed to investigate if levodopa/benserazide treatment improves recovery of lost neurological function and contributes to tissue reorganization in the rat brain after stroke.
Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (120 minutes) and treated with levodopa (1, 5, and 20 mg/kg)/benserazide (15 mg/kg) or saline for 12 consecutive days starting on Day 2 after transient occlusion of the middle cerebral artery. Infarct volume was determined and sensorimotor function was assessed using the rotating pole test, a 28-point neuroscore, and a cylinder test on Days 2, 7, and 14 after transient occlusion of the middle cerebral artery. The spatiotemporal expression pattern of dopamine-1 and dopamine-2 receptors and the dopamine- and cAMP-regulated neuronal phosphoprotein in reactive astrocytes were analyzed in the ischemic hemisphere as well as in cultured astrocytes.
Treatment with levodopa/benserazide significantly improved the recovery of sensorimotor function after transient occlusion of the middle cerebral artery without affecting the infarct volume. In addition, we found that different subpopulations of glial fibrillary acidic protein-positive astrocytes in the peri-infarct area express dopamine-1 receptors and dopamine-2 receptors as well as dopamine- and cAMP-regulated neuronal phosphoprotein.
Our results strongly corroborate the concept of recovery enhancing actions of levodopa treatment after stroke. Also, astrocytes in the peri-infarct area may contribute to the dopamine enhanced recovery mechanisms.
对卒中患者给予左旋多巴/苄丝肼治疗会延迟治疗，这反而有助于增强功能恢复，但其中涉及的机制尚不清楚。本研究旨在探讨左旋多巴/苄丝肼治疗是否能改善卒中后大鼠丧失的神经功能恢复，并有助于脑组织的重组。
雄性 Wistar 大鼠接受短暂性大脑中动脉闭塞（120 分钟），并在大脑中动脉短暂闭塞后第 2 天开始连续 12 天给予左旋多巴（1、5 和 20mg/kg）/苄丝肼（15mg/kg）或生理盐水治疗。通过旋转杆试验、28 分神经评分和大脑中动脉短暂闭塞后第 2、7 和 14 天的圆筒试验评估梗死体积和感觉运动功能。在缺血半球以及培养的星形胶质细胞中分析多巴胺-1 和多巴胺-2 受体以及多巴胺和 cAMP 调节的神经元磷蛋白在反应性星形胶质细胞中的时空表达模式。
左旋多巴/苄丝肼治疗可显著改善大脑中动脉短暂闭塞后的感觉运动功能恢复，而不影响梗死体积。此外，我们发现梗死周围区不同亚群的胶质纤维酸性蛋白阳性星形胶质细胞表达多巴胺-1 受体和多巴胺-2 受体以及多巴胺和 cAMP 调节的神经元磷蛋白。
我们的结果强烈支持卒中后左旋多巴治疗增强恢复作用的概念。此外，梗死周围区的星形胶质细胞可能有助于多巴胺增强的恢复机制。
