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Immunohistochemical changes of the blood‐brain barrier in rat spinal cord after heavy‐ion irradiation
Author(s) -
Okada S,
Okeda R,
Matsushita S,
Kawano A
Publication year - 1998
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.1998.tb00099.x
Subject(s) - white matter , pathology , blood–brain barrier , spinal cord , immunostaining , necrosis , tight junction , medicine , biology , immunohistochemistry , anatomy , central nervous system , endocrinology , magnetic resonance imaging , microbiology and biotechnology , psychiatry , radiology
Changes in the blood‐brain barrier (BBB) of the rat spinal cord after irradiation with heavy ion were investigated ultrastructurally and immunohistochemically by using SMI 71, a monoclonal antibody against rat endothelial barrier antigen (EBA); anti‐ZO‐1, a polyclonal antibody against endothelial tight junctions, anti‐rat serum to extravasated serum, and anti‐vascular endothelial growth factor (VEGF). The lower thoracic and lumbar cord of male Wistar rats was singly irradiated with a carbon beam at a dose of 30 Gy. Rats were sacrificed before or after the onset of hind limb paralysis. Histologically, white‐matter vacuolization was observed from 13 weeks after irradiation, and white‐matter necrosis was first noted at 17 weeks. SMI 71 staining was decreased or lost 13 weeks after irradiation, just prior to the formation of white‐matter necrosis, and was almost completely lost in the center and periphery of the white‐matter necrosis. Although ZO‐1 expression and tight junctions in the ultrastructure were preserved at that time, serum leakage occurred almostly completely in parallel with the changes in EBA. Therefore, carbon‐ion irradiation at a dose of 30 Gy induces BBB breakdown 13 weeks after irradiation. The SMI 71‐negative blood vessels were sparsely distributed throughout the entire white and gray matter, and there was no evidence of preferential localization. Immunostaining of smooth muscle actin showed that most of the SMI 71‐negative blood vessels were veins or capillaries. These findings suggest that the hyper‐permeability of the veins and/or capillaries that occurs after a certain latent period is one of the important factors in the pathogenesis of delayed radiation injury by carbon ions, the same as by X‐rays. Radiation‐induced functional disturbances of the endothelium and involvement of cytokines such as VEGF are suspected of being the cause of such vascular hyper‐permeability.