Treatment with Mesenchymal-Derived Extracellular Vesicles Reduces Injury-Related Pathology in Pyramidal Neurons of Monkey Perilesional Ventral Premotor Cortex

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Figure 1.
Figure 1.

Experimental design and measurement of passive membrane properties of vPMC pyramidal neurons. A, Experimental workflow: Monkeys were first behaviorally assessed using our HDT (left panel) before and after cortical injury (arrow, middle panel), as described previously (Moore et al., 2019). The monkeys were randomly assigned to receive either vehicle or EV treatment, and then the rate and degree of behavioral recovery of preoperative grasp pattern and latency were assessed. Recovery data (adapted from Moore et al., 2019) show the number of days to recover, which was fewer (faster rate) in EV compared with vehicle-treated monkeys (t test, p < 0.01). At 14-16 weeks after injury, acute slices were harvested during perfusion with Kreb's buffer from vPMC (vPMCveh vs vPMCEV). Location of tissue block harvested containing vPMC (area 6Vb) immediately ventral to the lesion (A, arrow) and the estimated boundary between vPMC (area 6Va and 6Vb) and ventral M1 (vM1) are shown on the lateral surface of rhesus monkey brain. Whole-cell patch-clamp recording and intracellular filling of layer 3 vPMCveh (n = 69 neurons from 4 monkeys) and vPMCEV (n = 39 neurons from 2 monkeys) neurons were employed. Data from vPMC were compared with neurons harvested from vPMC of nonlesionedaged-matched control brains (vPMCnonlesioned; n = 22 neurons from 2 monkeys) from a cohort of monkeys in a separate study. B, Lateral surface of brain maps (left insets) shows the sampling location and 2D plots of recorded cells (white box), and sampling location of tissue analyzed for c-fos labeling experiments (black box; n = 5 EV-treated, n = 5 vehicle-treated monkeys). Representative epifluorescence images (right panels) show coronal vPMC slices from which recordings were obtained, which were labeled with SMI-32+ after fixation to verify cytoarchitecture. Note the strong band of SMI32+ label in layer 3 (L3) and 5 (L5). The absence of large SMI32+ Betz cells in L5 is consistent with the cytoarchitecture of vPMC. C, Representative traces of voltage responses to a series of 200 ms current pulses. D, Box-and-whisker and vertical scatter plots of Vr, taum, and Rn. E, Within-group linear relationships of membrane tau versus Rn.

  1. The Journal of Neuroscience vol. 40 no. 17 3385-3407
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