To explore the effect of transcranial alternating current stimulation combined with exercise training on functional recovery in rats with limb spasm after cerebral infarction based on hypoxic inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway.

Out of 50 SPF grade SD male rats, 10 rats were selected as the normal (NO) group using a random number table method, while the remaining 40 rats were used to establish rat models of limb spasm after cerebral infarction by suture method combined with internal capsule injection of N-methyl-D-aspartic acid. Among them, 30 rats were successfully prepared. The model rats were randomly divided into a normal (NO) group, a model (MO) group, a combined (UN) group, and a combined+HIF-1α/VEGF pathway inhibitor (UH) group using a random number table method, with 10 rats in each group. The UN group received transcranial alternating current stimulation combined with exercise training intervention, while the UH group received intraperitoneal injection of HIF-1α/VEGF pathway inhibitor at a dose of 16 mg/kg on top of the UN group. The NO group and MO group did not receive treatment. After the treatment, Zea-Longa score, modified Ashworth score, Feeney balance test, and screen test were used to evaluate functional recovery. HE staining was used to detect the pathological morphology of brain tissue, and RT-PCR and immunoblotting were used to detect the expression of HIF-1α/VEGF pathway in brain tissue.

The Zea-Longa score, modified Ashworth score, Feeney balance test score and screen test score were compared among the four groups of rats after intervention, and the differences were statistically significant (P<0.05); Moreover, the NO group<UN group<UH group<MO group, and the differences of pairwise comparison among four groups were statistically significant (P<0.05). The HE staining results showed that, the brain tissue structure of the NO group is intact, and the distribution of nerve cells is uniform; The brain tissue structure of the MO group was damaged, showing edema of the brain tissue, disordered distribution of nerve cells, and nuclear atrophy; Improvement of pathological structure: UN group>UH group>MO group. The mRNA and protein expression of HIF-1α and VEGF in the brain tissues of four groups of rats were compared, and the differences were statistically significant (P<0.05); The expression levels of HIF-1α/VEGF mRNA in brain tissue were compared, with MO group<NO group<UH group<UN group, and the differences of pairwise comparison among four groups were statistically significant (P<0.05); The expression levels of HIF-1α and VEGF proteins were compared, with MO group<UH group<UN group<NO group, and the differences of pairwise comparison among four groups were statistically significant (P<0.05).

Transcranial AC stimulation combined with exercise training has a significant effect on the functional recovery of rats with limb spasm after cerebral infarction, and can effectively improve the nerve function and limb function of rats, which may be related to the regulation of HIF-1α/VEGF pathway.