The effects of paired associative stimulation of tibial nerve-M1 cortex on forelimb dysfunction in rats with cerebral ischemic stroke and the underlying mechanisms

Abstract

Objective To explore the effects and the underlying mechanisms by which paired associative stimulation (PAS) of tibial nerve electrostimulation and M1 cortex transcranial magnetic stimulation (TMS) in promoting the recovery of forelimb dysfunction in rats with cerebral ischemic stroke. Methods Resting motor thresholds of left extensor carpi radialis muscle (ECR) were determined 5 min before and 5 min, 30 min, 60 min after PAS, respectively, in 8 male Sprague-Dawley (SD) rats. Then 48 male SD rats were divided into a sham group (n=16) subject to sham surgery, an experimental group (n=32) which was further divided into a MCAO group (n=16) and a PAS group (n=16) after cerebral ischemic stroke model was established successfully by occluding the right middle cerebral artery. 24 hours after surgery, PAS consisting of left tibial nerve stimulation and right M1 cortex area TMS was applied to PAS group once daily for 7 consecutive days. The corner tests and grip strength tests were performed before and after 7 days of PAS treatment in each group. The RMTs of left ECR were determined, metabolites of the left area tissue of cervical spinal cord were measured by nuclear magnetic resonance spectrum, and expressions of Bcl-2 and Bax of left and right area tissue of cervical spinal cord enlargement were detected by Western Blot technique after 7 days of intervention. Results The average RMTs of left ECR at 5 min, 30 min, 60 min after PAS were significantly lower than those at 5 min before PAS (P<0.05). All rats in experimental group showed significant higher turning scores and lower grip strength when compared with sham group (P<0.001 or P<0.01). After PAS intervention, PAS group demonstrated lower turning scores, higher grip strength and lower RMT of left ECR as compared with MCAO group (P<0.05 or P<0.01). The expression of GABA of left cervical enlargment was significantly decreased in MCAO group when compared with the sham group (P<0.05), and there was no significant difference between MCAO group and PAS group. Meanwhile, other metabolites showed no significant difference among the three groups. The average expression level of Bcl-2 and Bax proteins in both sides of cervical spinal cord enlargment showed no significant difference among three groups either. Conclusions Tibial nerve-M1 cortex area PAS may increase the excitability of motor cortical representation of forelimbs in rats, by which PAS promotes the recovery of forelimb dysfunction in rats with cerebral ischemic stroke. Key words: Cerebral ischemic stroke; Paired associative stimulation; Resting motor threshold; GABA