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The blood-brain barrier (BBB) represents the interface between the brain and other body tissues. Its ability to protect the brain from harmful compounds has attracted the attention of clinicians and investigators, but far from being a simple physical barrier, the BBB is a complex, heterogeneous, and dynamic tissue. The integrated function of the cerebral microvasculature, tight junction proteins, brain microvascular endothelial cells (BMECs), cellular transport pathways, and enzymatic machinery jointly contribute to normal BBB integrity. Aging, systemic diseases, and ischemic injury can disrupt these processes, resulting in a decline in overall BBB function and integrity. Based on the published literature, this study proposes that age- and disease-related BBB alterations play a key role in diminishing the ability of older patients to recover from acute ischemic stroke. Evidence linking deficits in the cerebral microvasculature and BBB integrity to dementia, medication-related cognitive decline, white matter disease (WMD or leukoaraiosis), and related geriatric syndromes including delirium, gait disorders, and urinary incontinence is also reviewed. Priority areas for a future research agenda include strategies to improve clinicians' ability to diagnose, prevent, and manage BBB abnormalities. In future years, in vivo measures such as functional and contrast-enhanced neuroimaging will be used to evaluate BBB integrity in older adults while also assessing the effectiveness of interventions, some targeting inflammatory pathways known to disrupt the BBB, for their ability to prevent or slow the progression of these complex multifactorial geriatric syndromes., (© 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.)

A simplified protocol for isolating brain microvessel endothelial cells (BMEC) from human cortex and culturing them on a thick collagen plug is described. This method results in the establishment of monolayers of BMEC that retain numerous properties indicative of the blood-brain barrier (BBB) phenotype, such as elevated transendothelial electrical resistance, attenuated paracellular flux of sucrose, peripheral actin filament distribution and asymmetric localization of the efflux peptide, P-glycoprotein, to the apical (luminal) BMEC surface. The novel 3-dimensional nature of this model system renders it ideally suitable for assaying such varied aspects of BBB physiology as solute transport, pathogen penetrance, leukocyte infiltration and tumor metastasis into the brain. Moreover, the fact that the system is derived from human brain allows for the study of pathogenetic mechanisms that may only be operative in humans.

Brain microvessel endothelial cells (BMEC) exhibit the tendency to migrate through 3.0-vm pore semipermeable inserts and establish monolayers on both apical and basal filter surfaces. This can potentially lead to complications in accurately assessing a wide variety of physiologic parameters uniquely associated with these cells. To avoid this problem, we have explored growing BMEC on Transwell filters coated with hydrated collagen gels. BMEC seeded on such gels grow as a monolayer until confluency, but do not invade the subendothelial collagen matrix or the underlying support filter. Furthermore, BMEC grown in this manner exhibit biochemical, morphologic, and electrophysiologic properties reflective of the endothelial cells that comprise the blood-brain barrier in vivo. Although the collagen gel acts as an impenetrable barrier to BMEC, and thus ensures the growth of only a single layer of cells, it nevertheless can be infiltrated by monocytes that have been stimulated by a chemotaxin to undergo diapedesis. Thus, growing BMEC on collagen gel-coated Transwells has broad applications for the in vitro study of both blood-brain barrier physiology as well as the mechanisms underlying central nervous system inflammation.

The article presents abstracts of research papers about blood brain barrier and its role in immune privilege in the CNS in health and disease. They include "Heterogeneity of the CNS microvasculature," "Reactive oxygen species and pathological events in multiple sclerosis," "Dendritic cell migration across the blood-brain barrier is mediated via tight junctions in mmp-dependent way," and "Blood-brain barrier transmigration of human monocytes induces their differentiation into dendritic cells."

Abstract Background Production of the chemokine CCL2 by cells of the neurovascular unit (NVU) drives critical aspects of neuroinflammation. Suppression of CCL2 therefore holds promise in treating neuroinflammatory disease. Accordingly, we sought to determine if the compound bindarit, which inhibits CCL2 synthesis, could repress the three NVU sources of CCL2 most commonly reported in neuroinflammation – astrocytes, microglia and brain microvascular endothelial cells (BMEC) – as well as modify the clinical course of neuroinflammatory disease. Methods The effect of bindarit on CCL2 expression by cultured murine astrocytes, microglia and BMEC was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bindarit action on mouse brain and spinal cord in vivo was similarly investigated by qRT-PCR following LPS injection in mice. And to further gauge the potential remedial effects of bindarit on neuroinflammatory disease, its impact on the clinical course of experimental autoimmune encephalomyelitis (EAE) in mice was also explored. Results Bindarit repressed CCL2 expression by all three cultured cells, and antagonized upregulated expression of CCL2 in both brain and spinal cord in vivo following LPS administration. Bindarit also significantly modified the course and severity of clinical EAE, diminished the incidence and onset of disease, and evidenced signs of disease reversal. Conclusion Bindarit was effective in suppressing CCL2 expression by cultured NVU cells as well as brain and spinal cord tissue in vivo. It further modulated the course of clinical EAE in both preventative and therapeutic ways. Collectively, these results suggest that bindarit might prove an effective treatment for neuroinflammatory disease.