Calcium channel blockade with nimodipine reverses MRI evidence of cerebral oedema following acute hypoxia

• Published in: Journal of cerebral blood flow and metabolism Vol. 39; no. 2; pp. 285 - 301
• Main Authors: Rowland, Matthew J, Ezra, Martyn, Winkler, Anderson, Garry, Payashi, Lamb, Catherine, Kelly, Michael, Okell, Thomas W, Westbrook, Jon, Wise, Richard G, Douaud, Gwenaëlle, Pattinson, Kyle TS
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.02.2019
• Subjects: Adult; Brain Edema - diagnostic imaging; Brain Edema - drug therapy; Brain Edema - etiology; Brain Edema - metabolism; Calcium - metabolism; Calcium Channel Blockers - administration & dosage; Calcium Signaling - drug effects; Female; Humans; Hypoxia, Brain - complications; Hypoxia, Brain - diagnostic imaging; Hypoxia, Brain - drug therapy; Hypoxia, Brain - metabolism; Magnetic Resonance Imaging; Male; Nimodipine - administration & dosage; Original; Thalamus - diagnostic imaging; Thalamus - metabolism; hypoxia; calcium; MRI; nimodipine; Apparent diffusion coefficient
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X17726624

Acute cerebral hypoxia causes rapid calcium shifts leading to neuronal damage and death. Calcium channel antagonists improve outcomes in some clinical conditions, but mechanisms remain unclear. In 18 healthy participants we: (i) quantified with multiparametric MRI the effect of hypoxia on the thalamus, a region particularly sensitive to hypoxia, and on the whole brain in general; (ii) investigated how calcium channel antagonism with the drug nimodipine affects the brain response to hypoxia. Hypoxia resulted in a significant decrease in apparent diffusion coefficient (ADC), a measure particularly sensitive to cell swelling, in a widespread network of regions across the brain, and the thalamus in particular. In hypoxia, nimodipine significantly increased ADC in the same brain regions, normalizing ADC towards normoxia baseline. There was positive correlation between blood nimodipine levels and ADC change. In the thalamus, there was a significant decrease in the amplitude of low frequency fluctuations (ALFF) in resting state functional MRI and an apparent increase of grey matter volume in hypoxia, with the ALFF partially normalized towards normoxia baseline with nimodipine. This study provides further evidence that the brain response to acute hypoxia is mediated by calcium, and importantly that manipulation of intracellular calcium flux following hypoxia may reduce cerebral cytotoxic oedema