Validation of Monro-Kellie doctrine during blood pressure lowering in mice using fNIRS

Abstract

The Monro-Kellie doctrine states that the sum of the contents of the intracranial cavity is constant, and consequently dynamics of blood and cerebrospinal fluid (CSF) volumes should be in an anti-correlation relationship. This phenomenon helped to explain many abnormalities in intracranial hypotension and CSF depletion. We aimed to validate the same phenomenon in mice during a blood pressure (BP) lowering test. Eight 2-3-month-old C57/Bl6N (Charles River) female mice were used in this study. We used both nicardipine hydrochloride and sodium nitroprusside (SNP) infusion into the femoral vein to lower the BP. A multi-wavelength NIRS (685, 830, and 980 nm) measuring hemoglobin and water concentrations, sampled at 800 Hz, was used. The fiber probes for the light source and detector were inserted into the ear canals and positioned towards the brain, giving a distance of approximately 1 cm. Following the Monro-Kellie doctrine, the blood volume, i.e., total hemoglobin (HbT), and CSF volume should be in an anti-correlation relationship. Our experiments showed that concentration changes of total hemoglobin (HbT) and water, are in anti-correlation with correlation coefficients of -0.991 ± 0.007.