Effects of HF-rTMS on microglial polarization and white matter integrity in rats with poststroke cognitive impairment

Abstract

Poststroke cognitive impairment (PSCI) occurs frequently after stroke, but effective treatments are lacking. Previous studies have revealed that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has a beneficial effect on PSCI, but the mechanism is unclear. This study aimed to evaluate the effect of 10 and 20 Hz HF-rTMS on PSCI and the possible mechanisms. An ischemic stroke rat model was established by transient middle cerebral artery occlusion (tMCAO). The modified neurological deficit score (mNSS) and Morris water maze tests were conducted to assess neurological function and cognitive function. Luxol Fast Blue (LFB) staining was performed to evaluate white matter damage. Proinflammatory and anti-inflammatory cytokines were measured using enzyme-linked immunosorbent assays (ELISA). Immunofluorescence was used to assess microglial activation and polarization. Western blotting was performed to measure JAK2-STAT3 pathway-related protein expression. We found that HF-rTMS decreased the neurological deficit score. Compared with 10 Hz HF-rTMS, 20 Hz HF-rTMS more markedly improved the cognitive function of tMCAO rats at day 28 after operation. Furthermore, 20 Hz HF-rTMS attenuates white matter lesion, decreased proinflammatory cytokine levels, and increased anti-inflammatory cytokine levels. It also decreased the number of CD68- and CD16/32-positive microglia and increased the number of CD206-positive microglia. In addition, p-JAK2, JAK2, p-STAT3 and STAT3 expression was increased. These findings suggest that HF-rTMS improves cognitive function and attenuates white matter lesion in tMCAO rats by shifting microglia toward the M2 phenotype. Mechanisms may be related to regulation JAK2-STAT3 pathways.