Summary
We induced chronic relapsing experimental allergic encephalomyelitis (EAE), and studied the ultrastructural and ultracytochemical changes of the blood-brain barrier (BBB) in the demyelinating lesions of various stages of EAE. In the chronic, inactive stage with gliosis and perivascular fibrosis, the basal lamina (BL) of the perivascular processes of astrocytes was formed only partially, and neural parenchyma was not fully separated from the perivascular mesenchymal tissues by the BL of astrocytic processes. Vascular permeability of the BBB was studied using exogenous horseradish peroxidase (HRP) as the tracer: HRP extravasation was marked during the stages of both active myelin breakdown and removal of debris, and was recognized even at the inactive stage, although the degree was reduced to a very low level. The functions of the endothelia, assessed by ouabain-sensitive, K+-dependentp-nitrophenylphosphatase activity, were impaired as EAE progressed. The decrease in HRP leakage at the inactive stage suggests the endothelial impairment of active transport of metabolites including HRP. Along with the development of infammatory demyelination in EAE, the BBB in affected areas became more and more altered, and gradual morphological and functional impairment of the BBB developed.
Similar content being viewed by others
References
Autilio LA, Norton WT, Terry RD (1964) The preparation and some properties of purified myelin from the central nervous system. J Neurochem 11:17–27
Betz AL, Firth JA, Goldstein GW (1980) Polarity of the blood-brain barrier: distribution of enzymes between and the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res 192:17–28
Cereijido M, Ehrenfeld J, Meza I, Martínez-Palomo A (1980) Structural and functional membrane polarity in cultured monolayers of MDCK cells. J Membr Biol 52:147–159
Cervós-Navarro J, Artigas J, Mršulja BJ (1983) Morphofunctional aspects of the normal and pathological blood-brain barrier. Acta Neuropathol (Berl) [Suppl], 8:1–19
Dragsten PR, Blumenthal R, Handler JS (1981) Membrane asymmetry in epithelia: is the tight junction a barrier to diffusion in the plasma membrane? Nature 294:718–722
Farquhar MG, Palade GE (1963) Junctional complexes in various epithelia. J Cell Biol 17:375–412
Galli P, Brenna A, De Camilli P, Meldolesi J (1976) Extracellular calcium and the organization of tight junctions in pancreatic acinar cells. Exp Cell Res 99:178–183
Graham RC Jr, Karnovsky MJ (1966) The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem 14:291–302
Hirano A (1981) A guide to neuropathology, 1st edn. Igaku-Shoin, New York Tokyo, pp. 204–224
Kato S, Nakamura H (1987) Ultracytochemical localization of alkaline phosphatase activity in endothelial cells in chronic relapsing experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 73:220–226
Kato S, Nakamura H (1987) Localization of adenosine triphosphatase activity of the endothelia in chronic relapsing experimental allergic encephalomyelitis. J Neuroimmunol 16:273–282
Kitz K, Lassmann H, Karcher D, Lowenthal A (1984) Blood-brain barrier in chronic relapsing experimental allergic encephalomyelitis: a correlative study between cerebrospinal fluid protein concentrations and tracer leakage in the central nervous system. Acta Neuropathol (Berl) 63:41–50
Kristensson K, Wiśniewski HM (1977) Chronic relapsing experimental allergic encephalomyelitis: studies in vascular permeability changes. Acta Neuropathol (Berl) 39:189–194
Lassmann H (1983) Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple screlosis. Springer, Berlin, pp 1–95
Lewis BA, Gray GM, Coleman R, Michell RH (1975) Differences in the enzymic, polypeptide, glycopeptide, glycolipid and phospholipid compositions of plasma membranes from the two surfaces of intestinal epithelial cells. Biochem Soc Trans 3:752–753
Louvard D (1980) Apical membrane aminopeptidase appears at site of cell-cell contact in cultured kidney epithelial cells. Proc Natl Acad Sci USA 77:4132–4136
Mayahara H, Saito T, Hirano H, Ogawa K (1967) Electron microscopic demonstration of activities of adenosine triphosphatase (ATPase) and alkaline phosphatase (ALPase) using lead citrate. J Electron Microsc (Tokyo) 16:211–212
Mayahara H, Fujimoto K, Ando T, Ogawa K (1980) A new one-step method for the cytochemical localization of ouabain-sensitive, potassium-dependent p-nitrophenyl-phosphatase activity. Histochemistry 67:125–138
Meldolesi J, Castiglioni G, Parma R, Nassivera N, De Camilli P (1978) Ca++-dependent disassembly and reassembly of occluding junctions in guinea pig pancreatic acinar cells: effect of drugs. J Cell Biol 79:156–172
Peachey LD, Rasmussen H (1961) Structure of the toad's urinary bladder as related to its physiology. J Biophys Biochem Cytol 10:529–553
Pisam M, Ripoche P (1976) Redistribution of surface macromolecules in dissociated epithelial cells. J Cell Biol 71:907–920
Raine CS (1985) Experimental allergic encephalomyelitis and experimental allergic neuritis. Handb Clin Neurol 47:429–466
Sang ÜH, Saier MH Jr, Ellisman MH (1979) Tigh junction formation is closely linked to the polar redistribution of intramembraneous particles in aggregating MDCK epithelia. Exp Cell Res 122:384–391
Truex RC, Carpenter MB (1969) Human neuroanatomy, 6th edn. Williams & Wilkins, Baltimore, pp 12–25
Vorbrodt AW, Lossinsky AS, Wiśniewski HM (1982) Cytochemical localization of ouabain-sensitive, K+-dependent p-nitro-phenylphosphatase (transport ATPase) in the mouse central and peripheral nervous systems. Brain Res 243:225–234
Vorbrodt AW, Lossinsky AS, Wiśniewski HM (1983) Enzyme cytochemistry of blood-brain barrier (BBB) disturbances. Acta Neuropathol (Berl) [Suppl] 8:43–57
Wiśniewski HM, Keith AB (1977) Chronic relapsing experimental alleric encephalomyelitis: an experimental model of multiple sclerosis. Ann Neurol 1:144–148
Author information
Authors and Affiliations
Additional information
Supported in part by a grant (1988) from the Neuroimmunological Disorders Research Committee, the Ministry of Health and Welfare of Japan
Rights and permissions
About this article
Cite this article
Kato, S., Nakamura, H. Ultrastructural and ultracytochemical studies on the blood-brain barrier in chronic relapsing experimental allergic encephalomyelitis. Acta Neuropathol 77, 455–464 (1989). https://doi.org/10.1007/BF00687246
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00687246