The glymphatic system was impaired in spontaneously hypertensive rats

Abstract

Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure, which can be accompanied by functional impairment of or organic damage to the heart, brain, kidney and other organs. Hypertensive emergencies occur when significant increases in blood pressure result in persistent target organ damage. Hypertensive encephalopathy is a rare hypertensive emergency. Glymphatic system dysfunction is significantly correlated with the occurrence and development of hypertensive encephalopathy. We found that SHRs had a longer duration of peak contrast intensity and a slower clearance of contrast in the brain compared with WKY rats. Of note, in SHRs, there was a clear difference in contrast signal intensity between the hippocampus and the aqueduct. The results of cluster analysis showed that shr and WKY rats exhibited different patterns of voxel clustering. Progressively expanding brain clusters were observed from the posterior part of the brain near the cisterna magna (CM) to the anterior part of the brain, olfactory bulb, and dorsal cortical areas. In addition, shr showed a significant peak delay within some clusters and a slower rate of signal decay with time. Ex vivo imaging of ISF efflux showed that ISF efflux was also significantly reduced in shr. In vitro studies have shown decreased AQP4 expression in the brainstem and olfactory bulb of shr, accompanied by extensive astrogliosis, which may affect CSF circulation.Our study highlights the changes in glymphatic system function in a hypertension model and provides an important theoretical basis for further elucidating the mechanisms underlying the development and progression of hypertensive encephalopathy.