2017 Nov 10 – Stroke lesions with substantial unilateral cortex destruction allow very limited regaining of lost functions through plastic remodeling of neuronal networks, whereas assistive experimental approaches such as pharmacological treatments and transcranial stimulation are burdened with variability in cell targeting. To selectively activate intact corticospinal-projecting neurons contralateral to an ischemic lesion of the premotor and sensorimotor cortices corresponding to the preferred paw in adult rats, neurobiologists from Zurich, Switzerland, combined daily optogenetic stimulation starting early after stroke with subsequent intensive rehabilitative training. This led to the restoration of impaired forelimb movement patterns in a single pellet grasping task, as assessed by an unsupervised computer vision analysis of posture and kinematics developed at the Interdisciplinary Center for Scientific Computing, University of Heidelberg, Germany. Stimulated animals – with or without training – additionally performed significantly better than controls in two unfamiliar tasks of skilled forelimb usage. Functional rehabilitation positively correlated with fiber sprouting across the midline to the denervated cervical hemi-cord, together with fiber growth in the ipsilesional ventral corticospinal tract, as previosuly described in rats undergoing sequential treatment with anti-Nogo-A immunotherapy and intensive training.
In animals fully recovered under the latter protocol, optogenetically silencing neurons of the intact main motor forelimb area (M1) caused a significant drop in performance, suggesting their causal role.
Even though optogenetics requires invasive viral vector injections and implants of optic fibers, this study strongly encourages further research on high-resolution interventions to promote corticospinal rewiring for future stroke therapies.
