Parameter-optimized paired associative stimulation promotes neurological recovery following cerebral ischemia via modulation of oxidative stress and inflammation.

Objective: This study investigated whether parameter-optimized paired associative stimulation (PAS) could enhance neurological recovery after cerebral ischemia by modulating oxidative stress and inflammation in a rat middle cerebral artery occlusion (MCAO) model.

Methods: Twenty-four Sprague-Dawley rats were randomly divided into Sham, Model, PAS-ISI-10 ms, and PAS-ISI-15 ms groups. The MCAO model was established using the intraluminal filament method. PAS intervention (90 paired pulses/day for 28 days) was initiated 24 h postischemia. Neurological function was assessed using Longa scores, grip strength, and corner tests. Cerebral infarction (TTC staining), neuronal survival (Nissl staining), apoptosis (TUNEL), neuroregeneration markers (GAP43, BDNF, MAP2, and Syn), oxidative stress (GSH-Px and MDA), and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were evaluated.

Results: The PAS-ISI-10 ms group demonstrated significantly better neurological recovery than PAS-ISI-15 ms ( P  < 0.05), with reduced infarct volume ( P  < 0.01) and lower apoptosis rates ( P  < 0.01). Neuroregenerative markers showed greater upregulation in the 10 ms group ( P  < 0.05). Oxidative stress markers were significantly improved in PAS groups (GSH-Px increased P  < 0.01; MDA decreased P  < 0.01), with more pronounced effects in the 10ms condition. Proinflammatory cytokines were markedly reduced in both PAS groups ( P  < 0.05), showing stronger suppression in the 10ms group.

Conclusion: Parameter-optimized PAS with 10-ms ISI promotes neurological recovery after cerebral ischemia through coordinated antioxidant, anti-inflammatory, and neuroregenerative mechanisms. These findings provide evidence for optimizing noninvasive neuromodulation strategies in stroke rehabilitation.