High permeability of the CSF flow in the juvenile mouse brain by brain-wide DCE-MRI

Abstract

The vasculature system with a lymphatic function in the brain is manifested as meningeal lymphatic vessels and the glymphatic system, which drain waste products from cerebrospinal fluid (CSF) and produce interstitial fluid. Invasion of stimulated immune cells or inflammatory cytokines during the maturation is regarded as a sign of the disruption of brain functions through excessive immune stresses. However, it is unclear when the lymphatic system is functionally completed and in which parts of the organ the brain immunity is privileged (i.e., the blood-brain barrier is fully established). Here, we visualized the whole-head signal of gadolinium (Gd) contrast agents in mouse brains to investigate the CSF flow from the signals of Gd-contrast agents using magnetic resonance imaging (MRI) in the course of developmental stages. We found higher Gd-signals in the olfactory bulbs, prefrontal cortex, parietal surface regions of the neocortex along with dorsal meningeal lymphatic vessels, ventral midbrain, and a part of cerebellum, as well as in the basal brain regions, at the immature stage of postnatal (P) 4 weeks, compared to the P8-12 weeks. Our results suggest that the barrier of the vasculature system in mouse brains is still permeable until P1-month and small molecules can leak into the parenchyma.