Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, S-22184 Lund, Sweden.
LUBIN Lab-Lunds Laboratorium för Neurokirurgisk Hjärnskadeforskning, Division of Neurosurgery, Department of Clinical Sciences, Lund University, S-22184 Lund, Sweden.
Int J Mol Sci. 2021 Sep 23;22(19):10226. doi: 10.3390/ijms221910226.
Dopaminergic treatment in combination with rehabilitative training enhances long-term recovery after stroke. However, the underlying mechanisms on structural plasticity are unknown. Here, we show an increased dopaminergic innervation of the ischemic territory during the first week after stroke induced in Wistar rats subjected to transient occlusion of the middle cerebral artery (tMCAO) for 120 min. This response was also found in rats subjected to permanent focal ischemia induced by photothrombosis (PT) and mice subjected to PT or tMCAO. Dopaminergic branches were detected in the infarct core of mice and rats in both stroke models. In addition, the Nogo A pathway was significantly downregulated in rats treated with levodopa (LD) compared to vehicle-treated animals subjected to tMCAO. Specifically, the number of Nogo A positive oligodendrocytes as well as the levels of Nogo A and the Nogo A receptor were significantly downregulated in the peri-infarct area of LD-treated animals, while the number of Oligodendrocyte transcription factor 2 positive cells increased in this region after treatment. In addition, we observed lower protein levels of Growth Associated Protein 43 in the peri-infarct area compared to sham-operated animals without treatment effect. The results provide the first evidence of the plasticity-promoting actions of dopaminergic treatment following stroke.
多巴胺能治疗联合康复训练可增强中风后的长期恢复。然而，其对结构可塑性的潜在机制尚不清楚。在这里，我们在 Wistar 大鼠中观察到，在短暂性大脑中动脉闭塞（tMCAO） 120 分钟后，中风后第一周缺血区的多巴胺能神经支配增加。在光血栓形成（PT）诱导的永久性局灶性缺血大鼠和 PT 或 tMCAO 诱导的小鼠中也发现了这种反应。在两种中风模型的小鼠和大鼠的梗死核心中均检测到多巴胺能分支。此外，与 tMCAO 后给予左旋多巴（LD）治疗的大鼠相比，车辆处理的动物中 Nogo A 途径显著下调。具体而言，在 LD 治疗动物的梗死周围区域，Nogo A 阳性少突胶质细胞的数量以及 Nogo A 和 Nogo A 受体的水平均显著下调，而该区域的少突胶质细胞转录因子 2 阳性细胞数量增加。此外，与未治疗的假手术动物相比，我们在梗死周围区域观察到生长相关蛋白 43 的蛋白水平较低，且无治疗作用。这些结果首次提供了中风后多巴胺能治疗促进可塑性的证据。
