Where is the blood–brain barrier … really?

Abstract

Few terms in the biomedical lexicon are as widely recognized as the phrase blood-brain barrier (BBB). Indeed, it immediately conjures up a "barricade" between the blood and the brain, a feature often considered more obstacle than safeguard. In truth, the BBB performs in both capacities, and it is precisely this duality that imparts such a vital role to the BBB in influencing physiological and pathophysiological processes in the CNS. Although the concept is more than a century old, the BBB continues to remain enigmatic in both substance and idea, with seemingly resolved issues once again beckoning for clarification. In this regard, recent technological advancements, such as sequencing of the human genome and development of microarray analysis, have illuminated novel aspects of vascular gene expression and provoked reconsideration of the cellular and biochemical makeup of the BBB. In light of the critical impact of the BBB in the realms of science and medicine, this Mini-Review will revisit the topic of the composition of the BBB, specifically highlighting how recent developments in endothelial biology have prompted a reevaluation of its precise vascular location. We have intentionally avoided discussing generalized features of the BBB, as these have been skillfully described elsewhere as noted.

Differential axial localization along the mouse brain vascular tree of luminal sodium-dependent glutamine transporters Snat1 and Snat3

“…Although subpial arterioles and venules (10 to 100 mm diameter) along with capillaries (4 to 10 mm diameter) are found, only capillaries express the cohort of transport proteins required for vectorial BBB flux. Conversely, cultured endothelial cells from large non-BBB microvessels exhibit relatively rapid proliferation (Ge et al, 2005). Taken together with our previous gene expression study showing differential mRNA expression and regulation, our current localization data underscore the potential differing contributions of Snat3 and Snat1 to BBB transendothelial transport versus endogenous endothelial cellular metabolism, respectively.…”

A new method for determining blood–brain barrier integrity based on intracardiac perfusion of an Evans Blue–Hoechst cocktail

“…Some authors claim that responses of the BBB to pathological insults might be heterogeneous, varying along different segments of the brain vasculature and among different brain regions (Nitsch and Klatzo, 1983;Ge et al, 2005). Such claims support the methods that use brain sections to study BBB, such as ours, in contrast with those that process the tissue by mechanical disaggregation.…”

CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development

“…The analysis of CD146 expression suggests a heterogeneity between vascular segments with and without pericyte coverage within the vascular bed (arterioles/capillaries/venules). Capillaries constitute the largest and tightest fraction of the microvasculature (27,28). During early development of the BBB, the angiogenesis of mice brain capillary begins at embryonic day (E) 10, when the BECs enter the cortex and vascularize the CNS (1).…”