Deep cerebellar stimulation restores chronic motor deficits and loss of GABAergic neurons following sensorimotor cortex surgical brain injury in female rats

BACKGROUND: Acquired brain injury, whether the result of trauma, stroke, or iatrogenic complications, may cause persistent motor and cognitive deficits with limited effective treatments. Recent studies suggest that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) promotes long-term motor recovery after ischemic stroke and traumatic brain injury. Here, we examined the effect of LCN-DBS on motor recovery, and associated mechanisms, in an aspiration lesion model of surgical brain injury (SBI) in female rats. METHODS: Ten female Long-Evans rats underwent unilateral, catheter-assisted aspiration lesioning of sensorimotor cortex and DBS electrode implantation in the contralesional LCN. Three weeks post-SBI, rats were pseudo-randomly assigned to one of two experimental groups: SBI-sham DBS control (STIM-) and stimulation group (STIM+). The STIM+ group received 30 Hz LCN-DBS for six weeks. Motor performance was assessed pre- and post-SBI, as well as weekly during DBS, using the pasta matrix task, cylinder test, and horizontal ladder rung walking task. An additional five animals served as naïve controls for immunohistochemistry. RESULTS: Three weeks post-SBI, all lesioned animals demonstrated significant motor deficits. After six weeks of LCN-DBS, the STIM+ group demonstrated significant motor improvement compared to STIM- animals. IHC analysis revealed that STIM+ animals exhibited increased GAD67- and PV-positive GABAergic neurons compared to STIM- animals. CONCLUSION: LCN-DBS promotes motor recovery following SBI, potentially by modulating GABAergic neurotransmission in perilesional cortex. These findings further support LCN-DBS as a promising therapeutic intervention for motor rehabilitation following SBI, particularly in female subjects who are underrepresented in neuroscience research.