Repetitive transcranial magnetic stimulation improves cognitive impairment via the regulation of SDF-1α/CXCR4 axis in rats with ischemic stroke

Abstract

Post-stroke cognitive impairment(PSCI) is a common functional disorder after stroke, but effective therapies are limited. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, has been increasingly applied to aid recovery of cognitive function. Despite the wide application of rTMS in clinical researches, the underlying mechanisms remain largely undetermined. This study hypothesized that rTMS improves PSCI by regulating the expressions of SDF-1α/CXCR-4, which of vital significance in cerebral ischemia. An ischemic stroke rat model was established by transient middle cerebral artery occlusion(MCAO). The infarct volume was assessed by T2WI. DTI was conducted to evaluate white matter damage. Behavior tests including modified neurological severity scores(mNSS) and morris water maze(MWM) were performed. Western blotting and Real-Time PCR were performed to measure the expressions of the SDF-1α/CXCR4 in the ipsilateral brain. AMD3100 was used to confirm the effects of SDF-1α/CXCR4 signalling. The results showed that 10 Hz rTMS reduced cerebral infarct volumes and attenuated white matter lesion. Besides, 10 Hz rTMS improved the neurological recovery and cognitive deficits in rats with MCAO. In addition, 10Hz rTMS augmented the expression levels of the SDF-1α/CXCR4 axis after ischemic stroke. Furthermore, rTMS-induced functional improvements were abolished by the CXCR4 inhibitor AMD3100. Our research provides further evidence that 10 Hz rTMS could relieve structural impairments in the ipsilateral brain and alleviate PSCI after ischemic stroke, which was mightly associated with activating of SDF-1α/CXCR4 axis.