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Notes: Summary The organization of the cerebral ganglion of the shore crab Carcinus maenas, is investigated by conventional histological and electronmicroscopic techniques. This study forms part of a comprehensive survey of the blood-brain interface, particularly interesting in this group, as decapod Crustacea are unusual among invertebrates in possessing an intracerebral blood supply. Apart from the intracerebral blood vessels, tissue organization is closely similar to that observed in insect central neural ganglia. The ganglion is surrounded by the neural lamella, an acellular connective tissue sheath, probably containing mucopolysaccharide and collagen. A layer of specialised glia, the perineurium, immediately underlies the neural lamella, and appears to contribute to its formation. Large glia occupying a conspicuous cortical zone below the perineurium may be involved in glycogen metabolism and storage. Further morphologically distinct glial types are observed associated with neurones and blood vessels, but all neuroglia within the ganglion are probably of common origin. Neurone cell bodies are generally situated peripherally in groups, and send axons into neuropil (synaptic) areas in the ganglion core. Large lacunae in the cortical region and narrower 20 nm clefts deeper in the ganglion, constitute the interstitial space, and contain deposits of fibrillar material. Possible physiological implications are discussed.

Notes: Summary The structure of the cerebral ganglion of the shore crab, Carcinus maenas, is investigated by conventional electron miscroscope techniques, with particular emphasis on the relation of intracerebral blood vessels to other elements in the brain. The ganglion is permeated by a continuous network of channels which may be interpreted as invaginations of the ganglion surface. The afferent vessel (cerebral artery) is of mesodermal origin, but apparently terminates as an open-ended vessel soon after entering the brain, where it runs within the invaginated channels. The greater part of the cerebral vasculature, therefore, has no mesodermal endothelial lining. Tissue components in the diffusion path between blood and brain which could conceivably restrict diffusion, are the thick glial basement membrane, junctions between perivascular and between interstitial glia, and polymeric material in the extracellular space. However, apart from a barrier to large colloidal particles at the basement membrane, the present EM observations do not decisively pinpoint sites of diffusional restriction, nor can they be interpreted as evidence that such restriction exists.

Notes: Abstract 1. Unlike some interfaces between the blood and the nervous system (e.g., nerve perineurium), the brain endothelium forming the blood–brain barrier can be modulated by a range of inflammatory mediators. The mechanisms underlying this modulation are reviewed, and the implications for therapy of the brain discussed. 2. Methods for measuring blood–brain barrier permeability in situ include the use of radiolabeled tracers in parenchymal vessels and measurements of transendothelial resistance and rate of loss of fluorescent dye in single pial microvessels. In vitro studies on culture models provide details of the signal transduction mechanisms involved. 3. Routes for penetration of polar solutes across the brain endothelium include the paracellular tight junctional pathway (usually very tight) and vesicular mechanisms. Inflammatory mediators have been reported to influence both pathways, but the clearest evidence is for modulation of tight junctions. 4. In addition to the brain endothelium, cell types involved in inflammatory reactions include several closely associated cells including pericytes, astrocytes, smooth muscle, microglia, mast cells, and neurons. In situ it is often difficult to identify the site of action of a vasoactive agent. In vitro models of brain endothelium are experimentally simpler but may also lack important features generated in situ by cell:cell interaction (e.g. induction, signaling). 5. Many inflammatory agents increase both endothelial permeability and vessel diameter, together contributing to significant leak across the blood–brain barrier and cerebral edema. This review concentrates on changes in endothelial permeability by focusing on studies in which changes in vessel diameter are minimized. 6. Bradykinin (Bk)2 increases blood–brain barrier permeability by acting on B2 receptors. The downstream events reported include elevation of [Ca2+]i, activation of phospholipase A2, release of arachidonic acid, and production of free radicals, with evidence that IL-1β potentiates the actions of Bk in ischemia. 7. Serotonin (5HT) has been reported to increase blood–brain barrier permeability in some but not all studies. Where barrier opening was seen, there was evidence for activation of 5-HT2 receptors and a calcium-dependent permeability increase. 8. Histamine is one of the few central nervous system neurotransmitters found to cause consistent blood–brain barrier opening. The earlier literature was unclear, but studies of pial vessels and cultured endothelium reveal increased permeability mediated by H2 receptors and elevation of [Ca2+]i and an H1 receptor-mediated reduction in permeability coupled to an elevation of cAMP. 9. Brain endothelial cells express nucleotide receptors for ATP, UTP, and ADP, with activation causing increased blood–brain barrier permeability. The effects are mediated predominantly via a P2U (P2Y2) G-protein-coupled receptor causing an elevation of [Ca2+]i; a P2Y1 receptor acting via inhibition of adenyl cyclase has been reported in some in vitro preparations. 10. Arachidonic acid is elevated in some neural pathologies and causes gross opening of the blood–brain barrier to large molecules including proteins. There is evidence that arachidonic acid acts via generation of free radicals in the course of its metabolism by cyclooxygenase and lipoxygenase pathways. 11. The mechanisms described reveal a range of interrelated pathways by which influences from the brain side or the blood side can modulate blood–brain barrier permeability. Knowledge of the mechanisms is already being exploited for deliberate opening of the blood–brain barrier for drug delivery to the brain, and the pathways capable of reducing permeability hold promise for therapeutic treatment of inflammation and cerebral edema.