Postnatal remodeling of the leptomeningeal vascular network as assessed by intravital fluorescence video-microscopy in the rat

An intriguing characteristic of the ontogenic development of the cerebral vasculature is the rapid differentiation of the neonatal leptomeningeal vascular plexus into the mature, adult network form. The physiological and cellular mechanisms of this cerebrovascular remodeling process are unclear. The objective of this work was to determine and correlate changes in vascular density, network pattern and flow velocity in leptomeningeal microvessels of the rat during postnatal development in vivo. To this end, microvascular diameter, segment length, and vascular density of reconstructed leptomeningeal networks were measured from video-recordings of the microcirculation visualized through a cranial window in 0-15-day-old Sprague-Dawley rats. The velocity of erythrocytes in the microvessels was measured by frame to frame tracking of fluorescently labeled red blood cells. We found that surface vascular density (total vessel length per area), node density and segment density (object per area) decreased significantly by the second week after birth. Anastomosing vascular polygons, characteristic to newborn networks, became less numerous and larger in diameter during the postnatal 2-week period, indicating progressive rarefaction of the networks. Vessel diameter and red cell velocity showed transient increases at 1.5 weeks. The velocity/diameter ratio (V/D), an index of wall shear rate, increased by the age of 1.5 weeks and remained unchanged afterwards. There was a negative correlation between V/D and diameter at 1 week; this relationship was reversed to a positive correlation at 2 weeks. We conclude that postnatal remodeling of the leptomeningeal vascular network is associated with rarefaction and an adaptation of vessel caliber to wall shear rate. These changes may contribute to arterio-venous differentiation and redistribution of blood flow from the superficial to the intracortical vasculature in the developing brain.