The Human Cerebral Cortex Microvascular System: Development and Composition of the Meningeal and Intracerebral Extrinsic and Intrinsic (Blood-Brain Barrier) Compartments

Author(s):  
Miguel Marín-Padilla
1958 ◽  
Vol 195 (1) ◽  
pp. 7-22 ◽  
Author(s):  
Robert D. Tschirgi ◽  
J. Langdon Taylor

A slowly changing bioelectric potential difference (P.D.) is measured in rats, rabbits, cats and dogs between various regions of the central nervous system (CNS) and the blood within the jugular vein. It is shown that the CNS-blood P.D. is very sensitive to alterations in alveolar CO2 tension, but this relationship is dependent upon the H+ concentration rather than CO2 per se. Whereas increasing intravenous H+ concentration increases CNS positivity, topical application of acid solutions directly to the cerebral cortex decreases CNS positivity. The same relationship is found for intravenous and topical K+. Anoxia and circulatory failure produce CNS negative deflections, often exceeding 15 mv, which do not return to zero for over 24 hours after death. Simultaneous measurements of arterial blood pH, cerebral cortex pH and CNS-blood P.D. reveal the following relationship among these variables: ΔP.D. = κ Δ log10 [H+]a/[H+]i where [H+]a is the H+ concentration of the arterial blood and [H+]i is the H+ concentration of the CNS interstitial fluid. For the CNS-blood P.D. between cerebral cortex and jugular blood of rabbits and rats, κ is found to be 29 ± 5. These results are interpreted as indicating a source of emf across the pan-vascular blood-brain barrier which resembles a membrane diffusion potential. The blood-brain barrier is postulated to be more permeable to H+ and K+ than to anions and other cations.


1970 ◽  
Vol 3 (5) ◽  
pp. 293-302 ◽  
Author(s):  
A. Dereymaeker ◽  
L. Claeys ◽  
L. Sorel

2010 ◽  
Vol 298 (1) ◽  
pp. H179-H188 ◽  
Author(s):  
Grazyna B. Sadowska ◽  
Shadi N. Malaeb ◽  
Barbara S. Stonestreet

We examined the expression of tight junction (TJ) proteins in the cerebral cortex, cerebellum, and spinal cord of fetuses after maternal treatment with single and multiple courses of dexamethasone. Ewes received either single courses of four 6-mg dexamethasone or placebo injections every 12 h for 48 h between 104 and 107 days or the same treatment once a week between 76–78 and 104–107 days of gestation. TJ protein expression was determined by Western immunoblot analysis on tissue harvested at 105–108 days of gestation. Blood-brain barrier permeability has been previously quantified with the blood-to-brain transfer constant ( Ki) with α-aminoisobutyric acid ( 39 ). After a single course of dexamethasone, claudin-5 increased ( P < 0.05) in the cerebral cortex, occludin and claudin-1 increased in the cerebellum, and occludin increased in the spinal cord. After multiple dexamethasone courses, occludin and zonula occludens (ZO)-1 increased in the cerebral cortex, and occludin and claudin-1 increased in the cerebellum. Junctional adhesion molecule-A and ZO-2 expressions did not change. Linear regression comparing Ki to TJ proteins showed inverse correlations with claudin-1 and claudin-5 in the cerebral cortex after a single course and ZO-2 in the spinal cord after multiple courses and direct correlations with ZO-1 in the cerebellum and spinal cord after multiple courses. We conclude that maternal glucocorticoid treatment increases the expression of specific TJ proteins in vivo, patterns of TJ protein expression vary after exposure to single and multiple glucocorticoid courses, and decreases in blood-brain barrier permeability are associated with increases in claudin-1, claudin-5, and ZO-2 expression and decreases in ZO-1 expression. In utero glucocorticoid exposure alters the molecular composition of the barrier and affects fetal blood-brain barrier function.


2011 ◽  
Vol 505 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Andrew P. Viggars ◽  
Stephen B. Wharton ◽  
Julie E. Simpson ◽  
Fiona E. Matthews ◽  
Carol Brayne ◽  
...  

2019 ◽  
Vol 16 (4) ◽  
pp. 291-300 ◽  
Author(s):  
Siqueira M. da Silva ◽  
Gisbert D. Campos ◽  
Flávia C.A. Gomes ◽  
Joice Stipursky

Background: : In the developing cerebral cortex, Radial Glia (RG) multipotent neural stem cell, among other functions, differentiate into astrocytes and serve as a scaffold for blood vessel development. After some time, blood vessel Endothelial Cells (ECs) become associated with astrocytes to form the neurovascular Blood-Brain Barrier (BBB) unit. Objective: : Since little is known about the mechanisms underlying bidirectional RG-ECs interactions in both vascular development and astrocyte differentiation, this study investigated the impact of interactions between RG and ECs mediated by secreted factors on EC maturation and gliogenesis control. Method:: First, we demonstrated that immature vasculature in the murine embryonic cerebral cortex physically interacts with Nestin positive RG neural stem cells in vivo. Isolated Microcapillary Brain Endothelial Cells (MBEC) treated with the conditioned medium from RG cultures (RG-CM) displayed decreased proliferation, reduction in the protein levels of the endothelial tip cell marker Delta-like 4 (Dll4), and decreased expression levels of the vascular permeability associated gene, plasmalemma vesicle-associated protein-1 (PLVAP1). These events were also accompanied by increased levels of the tight junction protein expression, zonula occludens-1 (ZO-1). Result:: Finally, we demonstrated that isolated RG cells cultures treated with MBEC conditioned medium promoted the differentiation of astrocytes in a Vascular Endothelial Growth Factor-A (VEGF-A) dependent manner. Conclusion:: These results suggest that the bidirectional interaction between RG and ECs is essential to induce vascular maturation and astrocyte generation, which may be an essential cell-cell communication mechanism to promote BBB establishment.


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