Protection of metabolic-hemodynamic coupling by nimodipine in an animal model of cerebral small vessel disease.

Abstract

Cerebral small vessel disease (cSVD) impairs the physiological mechanisms that continuously match cerebral haemodynamics to metabolic need. We have monitored this impairment non-invasively employing in-house developed broadband near-infrared spectroscopy (bNIRS) and an animal model of cSVD, the spontaneously hypertensive stroke-prone rat (SHRSP). We also assessed the vasodilating agent, nimodipine, as a potential protective treatment. Male SHRSPs were randomly allocated at 3&#x2009;months of age to receive either a placebo or nimodipine diet. Both before and after 3&#x2009;months on diet, the changes in the concentration of oxyhaemoglobin (HbO), deoxyhaemoglobin (HHb) and oxidised cytochrome-c-oxidase (oxCCO) in the somatosensory cortex was obtained from the bNIRS recordings, and changes in blood oxygenation (HbDiff&#x2009;=&#x2009;HbO&#x2009;-&#x2009;HHb) and blood volume (HbT&#x2009;=&#x2009;HbO&#x2009;+&#x2009;HHb) were calculated. Metabolic-haemodynamic coupling was assessed by analysing the intrinsic slow wave oscillations of metabolic (oxCCO) and haemodynamic signals (HbO, HHb, HbT and HbDiff) at 0.02-0.06&#x2009;Hz, using wavelet coherence and semblance. Coherence and semblance were significantly (&#x2009;<&#x2009;0.001) reduced in aged SHRSPs, indicating impaired metabolic-haemodynamic coupling, but these measures were significantly (&#x2009;<&#x2009;0.001) protected by treatment with nimodipine. We reveal dysregulation of cerebral metabolic-haemodynamic coupling in SHRSP, and, importantly, demonstrate the protective effect of nimodipine, a drug suitable for clinical use in cSVD.