Blood-brain barrier permeability in CKD: Link with inflammation and cognitive and mood impairment in rats

Abstract

Chronic kidney disease (CKD) is associated with cognitive impairment. CKD is associated with increased permeability of the blood-brain barrier (BBB), resulting in increased cognitive impairment in animals and in humans. The aim of this study is to describe the inflammatory profile in blood and cerebro-spinal fluid (CSF) during a CKD model induced by adenine rich diet (ARD) in rats, in relation to BBB permeability and to explore the cognitive and mood impairment phenotypes. ARD rats displayed a 5-fold increase in BBB permeability, quantified with brain ^{99 m}Tc-DTPA SPECT/CT isotopic imaging, without alteration of brain perfusion. CKD is associated with increased PDGFRß levels in CSF (445 ± 85.6 vs. 303 ± 104.9 pg/mL, p = 0.03), suggesting pericyte dysfunction, but not with CSF levels of inflammatory cytokines, despite increased systemic inflammation. Neurobehavioural evaluation highlighted that ARD rats had impairment of short-term spatial memory, social memory and depressive features but not anxiety. In conclusion, CKD induces systemic inflammation and BBB permeability associated with pericyte dysfunction and alteration of memory and depressive features in rats. BBB disruption seems to be a crucial mechanism involved in cognitive and mood impairment during CKD.

Keywords: Blood-brain barrier; Chronic kidney disease; Cognitive impairment; Cytokines; Depression; Imaging.