Repetitive transcranial magnetic stimulation increases neurological function and endogenous neural stem cell migration via the SDF‑1α/CXCR4 axis after cerebral infarction in rats

Abstract

Neural stem cell (NSC) migration is closely associated with brain development and is reportedly involved during recovery from ischaemic stroke. Chemokine signalling mediated by stromal cell-derived factor 1α (SDF-1α) and its receptor CXC chemokine receptor 4 (CXCR4) has been previously documented to guide the migration of NSCs. Although repetitive transcranial magnetic stimulation (rTMS) can increase neurological function in a rat stroke model, its effects on the migration of NSCs and associated underlying mechanism remain unclear. Therefore, the present study investigated the effects of rTMS on ischaemic stroke following middle cerebral artery occlusion (MCAO). All rats underwent rTMS treatment 24 h after MCAO. Neurological function, using modified Neurological Severity Scores and grip strength test and NSC migration, which were measured using immunofluorescence staining, were analysed at 7 and 14 days after MCAO, before the protein expression levels of the SDF-1α/CXCR4 axis was evaluated using western blot analysis. AMD3100, a CXCR4 inhibitor, was used to assess the effects of SDF-1α/CXCR4 signalling. In addition, neuronal survival was investigated using Nissl staining at 14 days after MCAO. It was revealed that rTMS increased the neurological recovery of rats with MCAO, facilitated the migration of NSC, augmented the expression levels of the SDF-1α/CXCR4 axis and decreased neuronal loss. Furthermore, the rTMS-induced positive responses were significantly abolished by AMD3100. Overall, these results indicated that rTMS conferred therapeutic neuroprotective properties, which can restore neurological function after ischaemic stroke, in a manner that may be associated with the activation of the SDF-1α/CXCR4 axis.

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

“…Furthermore, cognitive functional recovery could arise from the elevated levels of SDF-1α and CXCR4 in ischemia rats [70]. Additionally, our prior study has shown that 10 Hz rTMS could signi cantly increase the protein expression levels of SDF-1α and CXCR4 in striatum in MCAO rats,which contributed to the restoration of motor function [23]. Evidence is accumulating that SDF-1α is involved in axonal path nding, outgrowth, and branching, while axonal sprouting occurs from the intact cortex into the peri-injured cortex and striatum [71].…”

“…Rats in the RA and MA groups received an AMD3100(medium saline; 2 mg/kg; i.p.) injection every other day since 2 days after MCAO until euthanasia according to previous reports [23].…”

“…Our prior study has shown that 10 Hz rTMS could signi cantly increase the protein expression levels of SDF-1α and CXCR4 in striatum, and promoted the migration of Neural stem cells(NSCs) in the subventricular zone (SVZ) after focal cerebral ischemia by regulating SDF-1α/CXCR4 axis [23]. Besides, one research have reported that electrical stimulation might modulate SDF-1α concentrations in ischemic stroke [24].…”

Cognitive Fitness: Harnessing the Strength of Exerkines for Aging and Metabolic Challenges

“…Moreover, SDF-1α facilitates the attraction of neural stem/progenitor cells (NSCs) towards the site of brain injury by engaging with its receptor, chemokine receptor type 4 (CXCR4). CXCR4 is predominantly found on neural stem/progenitor cells, and cells that express CXCR4 migrate in response to the concentration gradient of SDF-1α [ 151 , 152 ]. NSCs are responsible for neurogenesis and brain plasticity that could replace dead neurons [ 153 ].…”