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The blood–brain barrier (BBB) controls brain access of molecules and cells, communicates immune status to the central nervous system (CNS), and coordinates responses. Almost all solutes reach the brain from the blood through BBB transendothelial transporters that are often differentially localized on luminal and abluminal endothelial membranes. Therefore, BBB transporters crucially regulate CNS homeostasis and physiological responses to internal and external stimuli. Although the main functions of inflammatory processes are to remove the causes of the insult, to clear necrotic tissue, and to initiate tissue repair, these signals are often associated with further CNS damage in neuroinflammation. The BBB can aid adaptive responses; however, one hallmark of neuroinflammation is a breakdown of the tight endothelial barrier resulting in BBB opening, vascular leakage, and the loss of control over transendothelial transport. Thus, neuroinflammation often leads to pathological changes in CNS functions, such as those associated with the chronic age-related neuropathologies, Alzheimer’s disease and Parkinson’s disease, mechanical or physical insult and injury to the CNS (traumatic brain injury), infection, oncogenic diseases, and chronic autoimmune diseases, such as, multiple sclerosis and diabetes mellitus. Here, we review responses of selected ATP-binding cassette, solute carrier, receptor, and vesicular BBB endothelial transporters to neuroinflammatory mediators and diseases. Much emains to be learned concerning interactions of age, gender, genetics, microbiome, circadian cycle, diet, exercise, medication, etc., in neuroinflammatory processes. Crucially, in many regards, it is still unclear what tips the system from providing protective to effecting destructive responses.

Nogo is a member of the reticulon family. Our understanding of the physiological functions of the Nogo-A protein has grown over the last few years, and this molecule is now recognized as one of the most important axonal regrowth inhibitors present in central nervous system (CNS) myelin. Nogo-A plays other important roles in nervous system development, epilepsy, vascular physiology, muscle pathology, stroke, inflammation, and CNS tumors. Since the exact role of Nogo-A protein in human brain development is still poorly understood, we studied its cellular and regional distribution by immunohistochemistry in the frontal lobe of 30 human fetal brains. Nogo-A was expressed in the following cortical zones: ependyma, ventricular zone, subventricular zone, intermediate zone, subplate, cortical plate, and marginal zone. The number of positive cells decreased significantly with increasing gestational age in the subplate and marginal zone. Using different antibodies, changes in isoform expression and dimerization states could be shown between various cortical zones. The results demonstrate a significant change in the expression of Nogo-A during the development of the human brain. The effects of its time- and region-specific regulation have to be further studied in detail.

Cerebral cavernous malformations (CCMs) often cause hemorrhages that can result in severe clinical manifestations, including hemiparesis and seizures. The underlying mechanisms of the aggressive behavior of CCMs are undetermined to date, but alterations of vascular matrix components may be involved. We compared the localization of the tight junction proteins (TJPs) in 12 CCM specimens and the expression of glucose transporter 1 (GLUT-1), which is sensitive to alterations in TJP levels, in 5 CCM specimens with those in 5 control temporal lobectomy specimens without CCM by immunofluorescence microscopy. The TJPs occludin, claudin-5, and zonula occludens ZO-1 were downregulated at intercellular contact sites and partly redistributed within the surrounding tissue in the CCM samples; there was also a marked reduction of GLUT-1 immunoreactivity compared with that in control specimens. Corresponding analysis using quantitative real-time reverse transcription polymerase chain reaction on 8 CCM and 8 control specimens revealed significant downregulation of mRNA expression of occludin, claudin-5, ZO-1, and GLUT-1. The altered expression and localization of the TJPs at interendothelial contact sites accompanied by a reduction of GLUT-1 expression in dilated CCM microvessels likely affect vascular matrix stability and may contribute to hemorrhages of CCMs.