Concomitant enlargement of perivascular spaces and decrease in glymphatic transport in an animal model of cerebral small vessel disease

Abstract

Objectives: To observe glymphatic transport and evaluate enlarged perivascular spaces (PVSs) in spontaneously hypertensive rats (SHRs).

Methods: SHRs were used as an animal model of cerebral small vessel disease, and Wistar Kyoto (WKY) rats were used as the control group. Histopathology was used to evaluate the enlargement of PVSs. A fluorescent tracer was infused into the cisterna magna of rats, and the proportion of the brain parenchyma area exposed to the fluorescent tracer was later quantified to evaluate the influx and efflux function of the glymphatic system. The global and polarized expression of aquaporin protein 4 (AQP4) was analyzed by immunofluorescence.

Results: Compared with WKY rats, SHRs exhibited obviously enlarged PVSs and significantly decreased influx and efflux function of the glymphatic system. The results showed a significant decrease in AQP4 polarity in SHRs, but a difference in global AQP4 expression was not observed between SHRs and WKY rats.

Conclusions: Impaired glymphatic transport may be involved in the pathogenesis of arteriolosclerotic cerebral small vessel disease, and enlarged PVSs may be a manifestation of the impaired glymphatic system.

Keywords: Aquaporin 4; Cerebral small vessel disease; Glymphatic system; Perivascular space.