Calderazzo Samantha, Covert Margaret, Alba Diego De, Bowley Bethany E, Pessina Monica A, Rosene Douglas L, Buller Benjamin, Medalla Maria, Moore Tara L
Anatomy and Neurobiology Dept, BUSM, USA.
Center for Systems Neuroscience, BU, USA.
IBRO Neurosci Rep. 2022 Aug 18;13:243-254. doi: 10.1016/j.ibneur.2022.08.001. eCollection 2022 Dec.
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.
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，但作为治疗靶点的神经可塑性机制仍不清楚。我们团队最近的研究表明，对恒河猴初级运动皮层（M1）进行皮质损伤后，全身给予间充质干细胞衍生（MSCd）的细胞外囊泡（EVs），可使精细运动功能得到显著恢复，并减轻慢性炎症。在此，我们使用cfos（一种活性依赖的早期中间基因）免疫组织化学方法，标记存活的初级运动皮层和运动前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志物。与载体相比，EV治疗与M1深层中cfos锥体神经元密度增加、运动前区cfos抑制性中间神经元密度增加以及颈脊髓中MAP2 + 下运动神经元上的突触密度降低有关。这些数据表明，EVs的抗炎作用可能会减少与损伤相关的上运动神经元损伤和过度兴奋，以及颈脊髓中异常的代偿性重组，从而改善运动功能。
