Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
Cells. 2023 Jul 14;12(14):1859. doi: 10.3390/cells12141859.
Dopamine replacement therapy for Parkinson's disease is achieved using L-DOPA or dopamine D2/3 agonists, such as ropinirole. Here, we compare the effects of L-DOPA and ropinirole, alone or in combination, on patterns of glial and microvascular reactivity in the striatum. Rats with unilateral 6-hydroxydopamine lesions were treated with therapeutic-like doses of L-DOPA (6 mg/kg), an equipotent L-DOPA-ropinirole combination (L-DOPA 3 mg/kg plus ropinirole 0.5 mg/kg), or ropinirole alone. Immunohistochemistry was used to examine the reactivity of microglia (ionized calcium-binding adapter molecule 1, IBA-1) and astroglia (glial fibrillary acidic protein, GFAP), as well as blood vessel density (rat endothelial cell antigen 1, RECA-1) and albumin extravasation. L-DOPA monotreatment and L-DOPA-ropinirole cotreatment induced moderate-severe dyskinesia, whereas ropinirole alone had negligible dyskinetic effects. Despite similar dyskinesia severity, striking differences in perivascular microglia and astroglial reactivity were found between animals treated with L-DOPA vs. L-DOPA-ropinirole. The former exhibited a marked upregulation of perivascular IBA-1 cells (in part CD68-positive) and IBA-1-RECA-1 contact points, along with an increased microvessel density and strong perivascular GFAP expression. None of these markers were significantly upregulated in animals treated with L-DOPA-ropinirole or ropinirole alone. In summary, although ropinirole cotreatment does not prevent L-DOPA-induced dyskinesia, it protects from maladaptive gliovascular changes otherwise associated with this disorder, with potential long-term benefits to striatal tissue homeostasis.
帕金森病的多巴胺替代疗法采用 L-DOPA 或多巴胺 D2/3 激动剂，如罗匹尼罗。在这里，我们比较了 L-DOPA 和罗匹尼罗单独或联合使用对纹状体胶质细胞和微血管反应性模式的影响。单侧 6-羟多巴胺损伤的大鼠接受治疗剂量的 L-DOPA（6mg/kg）、等效的 L-DOPA-罗匹尼罗联合用药（L-DOPA 3mg/kg 加罗匹尼罗 0.5mg/kg）或罗匹尼罗单独治疗。免疫组织化学用于检测小胶质细胞（离子钙结合衔接分子 1，IBA-1）和星形胶质细胞（胶质纤维酸性蛋白，GFAP）的反应性，以及血管密度（大鼠内皮细胞抗原 1，RECA-1）和白蛋白外渗。L-DOPA 单一治疗和 L-DOPA-罗匹尼罗联合治疗诱导中度至重度运动障碍，而罗匹尼罗单独治疗几乎没有运动障碍作用。尽管运动障碍严重程度相似，但在接受 L-DOPA 治疗与 L-DOPA-罗匹尼罗联合治疗的动物之间，血管周围小胶质细胞和星形胶质细胞反应存在显著差异。前者表现出血管周围 IBA-1 细胞（部分 CD68 阳性）和 IBA-1-RECA-1 接触点的明显上调，同时微血管密度增加和强烈的血管周围 GFAP 表达。在接受 L-DOPA-罗匹尼罗或罗匹尼罗单独治疗的动物中，这些标志物均无明显上调。总之，尽管罗匹尼罗联合治疗不能预防 L-DOPA 诱导的运动障碍，但它可以防止与该疾病相关的适应性胶质血管变化，对纹状体组织稳态具有潜在的长期益处。
