Blood-brain barrier leakage in renovascular hypertensive rats: a quantitative MRI analysis

Abstract

Hypertension is a modifiable risk factor for cerebral small vessel disease (cSVD) which leads to blood-brain barrier (BBB) dysfunction. This study used gadolinium-enhanced MRI T1 and T2 in stroke-prone renovascular hypertensive rats (RHRSP) to quantify BBB leakage and brain lesions. Serum inflammation and endothelial disruption biomarkers were assessed. Brain aquaporin 4 (AQ4) and retinal morphology were evaluated by histology. RHRSP showed higher systolic blood pressure from the first post-surgical week (134.1 ± 16.6 vs 113.5 ± 11.4 mmHg; p=0.041). Gadolinium extravasation was increased in the whole brain of RHRSP (p<0.05), observing cerebral lesions in 50% of them. Regarding biomarkers, TNF-α was increased (13.5 ± 2.2 vs 11.1 ± 3.5 pg/ml, p=0.031) while soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) was lower (14.5 ± 2.2 vs 18.9 ± 2.5 pg/ml, p<0.001) in the acute hypertension phase. AQ4 was increased in the RHRSP brain (1.6 ± 0.7 vs 1.0 ± 0.2 NFU; p=0.001). Both retinal nuclear layers were reduced in RHRSP (p<0.05). Gadolinium-enhanced MRI allows the detection of BBB leakage during the establishment of RHRSP. BBB dysfunction is consistent with increased AQ4 and decreased sTWEAK release. Therefore, this animal model is useful for testing potential treatments at cSVD initial stages.