Continuous theta burst stimulation ameliorates cognitive deficits in microinfarcts mice via inhibiting glial activation and promoting paravascular CSF-ISF exchange.

Microinfarcts are widespread in the elderly, accompanied by varying degrees of cognitive decline. Continuous theta burst stimulation (cTBS) has been demonstrated to be neuroprotective on cognitive dysfunction, but the underlying cellular mechanism has been still not clear. In the present study, we evaluated the effects of cTBS on cognitive function and brain pathological changes in mice model of microinfarcts. The spatial learning and memory was assessed by Morris water maze (MWM), Glymphatic clearance efficiency was evaluated using in vivo two-photon imaging. The loss of neurons, activation of astrocytes and microglia, the expression and polarity distribution of the astrocytic aquaporin-4 (AQP4) were assessed by immunofluorescence staining. Our results showed that cTBS treatment significantly improved the spatial learning and memory, accelerated the efficiency of glymphatic clearance, up-regulated the AQP4 expression and improved the polarity distribution of AQP4 in microinfarcts mice. Besides, cTBS treatment increased the number of surviving neurons, whereas decreased the activated astrocytes and microglia. Our study suggested that cTBS accelerated glymphatic clearance and inhibited the excessive gliogenesis, which ultimately exerted neuroprotective effects on microinfarcts mice.