Neural recovery after cortical injury: Effects of MSC derived extracellular vesicles on motor circuit remodeling in rhesus monkeys.
Neural recovery after cortical injury: Effects of MSC derived extracellular vesicles on motor circuit remodeling in rhesus monkeys.
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DOI：
10.1016/j.ibneur.2022.08.001
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发表时间：
2022-12
影响因子：
1.5
通讯作者：
Moore, Tara L.
中科院分区：
文献类型：
--
作者：
Calderazzo, Samantha;Covert, Margaret;De Alba, Diego;Bowley, Bethany E.;Pessina, Monica A.;Rosene, Douglas L.;Buller, Benjamin;Medalla, Maria;Moore, Tara L.
关键词：
皮质和皮质脊髓束中运动回路的重组被认为是皮质损伤后功能恢复的基础，但可能成为治疗目标的神经可塑性机制仍不清楚。我们小组最近的工作表明，在恒河猴初级运动皮层（M1）受到皮质损伤后，使用间充质干细胞衍生（MSCd）细胞外囊泡（EV）进行全身治疗，可导致精细运动功能的强劲恢复并减少慢性炎症。在这里，我们使用 cfos（一种活动依赖性中间早期基因）的免疫组织化学来标记幸存的初级运动和前运动皮层中与任务相关的神经元，以及脊髓中轴突和突触可塑性的标记。与媒介物相比，EV 治疗与 M1 深层 cfos+ 锥体神经元密度更高、运动前区 cfos+ 抑制性中间神经元密度更高以及颈脊髓 MAP2+ 下运动神经元突触密度降低相关。这些数据表明，EV 的抗炎作用可能会减少损伤相关的上运动神经元损伤和过度兴奋，以及颈脊髓的异常代偿性重组，以改善运动功能。
Reorganization of motor circuits in the cortex and corticospinal tract are thought to underlie functional recovery after cortical injury, but the mechanisms of neural plasticity that could be therapeutic targets remain unclear. Recent work from our group have shown that systemic treatment with mesenchymal stem cell derived (MSCd) extracellular vesicles (EVs) administered after cortical damage to the primary motor cortex (M1) of rhesus monkeys resulted in a robust recovery of fine motor function and reduced chronic inflammation. Here, we used immunohistochemistry for cfos, an activity-dependent intermediate early gene, to label task-related neurons in the surviving primary motor and premotor cortices, and markers of axonal and synaptic plasticity in the spinal cord. Compared to vehicle, EV treatment was associated with a greater density of cfos+ pyramidal neurons in the deep layers of M1, greater density of cfos+ inhibitory interneurons in premotor areas, and lower density of synapses on MAP2+ lower motor neurons in the cervical spinal cord. These data suggest that the anti-inflammatory effects of EVs may reduce injury-related upper motor neuron damage and hyperexcitability, as well as aberrant compensatory re-organization in the cervical spinal cord to improve motor function.
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