Blood-Brain Barrier

Blood-Brain Barrier

1. Definition & overview

• The CNS is insulated from the periphery by a series of barriers that stringently regulate the movement of ions, molecules and cells between peripheral fluids (blood) and neural tissue, maintaining the tightly controlled extracellular environment required for neuronal homeostasis (G&G 14e Ch.17, p.327).
• These barriers control the influx of glucose and essential nutrients while greatly limiting entry of exogenous compounds, including most drugs — the central obstacle in CNS drug development (G&G 14e Ch.17, p.327).
• The three anatomical brain-barrier sites are: (1) the blood vessels that vascularize the CNS parenchyma (the BBB proper); (2) the meningeal coverings (arachnoid barrier + the endothelial barrier of subarachnoid-space vessels); and (3) the choroid plexus within the ventricles (G&G 14e Ch.17, p.327, Figure 17-1).
• The blood-brain barrier (BBB) is an endothelial barrier formed by the blood vessels vascularizing the CNS parenchyma; it constitutes most of the surface area of the brain barriers and is therefore the most important interface for drug delivery (G&G 14e Ch.17, p.327).
• The blood–CSF barrier (BCSFB) is an epithelial barrier formed by choroid plexus epithelial cells surrounding fenestrated ("leaky") plexus vessels; these cells tightly regulate the composition of the CSF they secrete into the ventricles (G&G 14e Ch.17, p.327).
• The arachnoid barrier is an epithelial barrier of arachnoid barrier cells that physically separates the fenestrated/leaky dura mater vessels from the subarachnoid space containing CSF (G&G 14e Ch.17, p.327).
• Functions of the barriers: insulate neurons from ionic fluctuations (preserving ion gradients for circuit function); protect the CNS from toxins, pathogens and the body's own immune system — critical because the CNS fails to regenerate after many injuries (G&G 14e Ch.17, p.327).
• The clinical importance of the barriers is underscored by the severe pathology of diseases in which they are disrupted — multiple sclerosis, stroke, traumatic brain injury (TBI), meningitis (G&G 14e Ch.17, p.327).
• Indian-PG framing (KDT): brain capillary endothelial cells have tight junctions and lack large paracellular spaces, and an investment of neural tissue (glial processes) covers the capillaries; together these constitute the blood-brain barrier. A similar blood-CSF barrier sits in the choroid plexus, where capillaries are lined by choroidal epithelium with tight junctions (KDT 8e Ch.2, pp.24–5).
• Both barriers are lipoidal: they limit entry of non-lipid-soluble drugs (e.g. streptomycin, neostigmine); only lipid-soluble drugs penetrate and act on the CNS (KDT 8e Ch.2, p.24).
• Quantitative scale of the BBB (human): vascular network ≈ 600 km long, endothelial wall thickness 200–400 nm, total surface area 15–25 m² — making the endothelium the primary blood–tissue interface for permeability, transport, coagulation and immune-cell infiltration (G&G 14e Ch.17, p.328; Wong et al., 2013).