Cerebrospinal fluid flow increases from newborn to adult stages

Abstract

Solute transport through the brain is of major importance for the clearance of toxic molecules and metabolites, and it plays key roles in the pathophysiology of the central nervous system. This solute transport notably depends on the cerebrospinal fluid (CSF) flow, which circulates in the subarachnoid spaces, the ventricles and the perivascular spaces. We hypothesized that the CSF flow may be different in the perinatal period compared to the adult period. Using in vivo magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF), we assessed the dynamic of the CSF flow in rodents at different ages. By injecting a contrast agent into the CSF, we first used MRI to demonstrate that CSF flow gradually increases with age, with the adult pattern observed at P90. This observation was confirmed by NIRF, which revealed an increased CSF flow in P90 rats when compared with P4 rats not only at the surface of the brain but also deep in the brain structures. Lastly, we evaluated the exit routes of the CSF from the brain. We demonstrated that indocyanine green injected directly into the striatum spread throughout the parenchyma in adult rats, whereas it stayed at the injection point in P4 rats. Moreover, the ability of CSF to exit through the nasal mucosa was increased in the adult rodents. Our results provide evidence that the perinatal brain has nonoptimal CSF flow and exit and, thus, may have impaired clean-up capacity. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018.

PDGF-B Is Required for Development of the Glymphatic System

“…Fluid transport in perivascular pathways has been implicated in clearance of solutes and proteins from the brain ( Iliff et al, 2012 ; Lundgaard et al, 2017 ; Mestre et al, 2018 ; Xie et al, 2013 ) but has been sparsely studied in development ( Di Palma et al, 2018 ). A recent MRI study demonstrated that the glymphatic system is developed by P90, although statistical significance was not indicated between P28 and P90 ( Di Palma et al, 2018 ). Because of the resolution limitations of MRI, our study adds a characterization of perivascular CSF influx in early postnatal ages.…”

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life

“…Early life is a critical period of brain development. Recent studies have shown that the glymphatic system in the rodent brain develops early in life 14,15 . For instance, Munk et al.…”

“…Recent studies have shown that the glymphatic system in the rodent brain develops early in life. 14,15 For instance, Munk et al found that glymphatic flow in the mouse brain gradually increased with age. They further found that glymphatic flow displayed initial signs in the circle of Willis at embryonic period 17.5, started in the HPC at P1, and ultimately matured at P14.…”

“…The glymphatic system develops early in life. For instance, the glymphatic flow in rat's brain develop by postnatal day 90 (P90) 14 . Similarly, the glymphatic flow in the mouse brain first emerges in the hippocampus (HPC) at P1 and is established in the cortex (CTX) at P14 15 .…”

Decreased Craniocervical CSF Flow in Patients with Normal Pressure Hydrocephalus: A Pilot Study

“…Prior studies have investigated the age dependency of CSF flow values, 14,31,[42][43][44][45] demonstrating age dependence of CSF flow parameter, 14,45 with significantly reduced CSF stroke volumes in the elderly. 31 However, Lokossou et al 44 suggested that aging mainly changes cerebral blood flow but preserves blood and CSF interactions, with an age-independent positive correlation between blood and CSF stroke volumes.…”