Toxin-Induced Vasogenic Cerebral Oedema in a Rat Model
Vasogenic cerebral oedema (VCO) was induced in Hooded Wistar rats by intraperitoneal injection of Clostridium perfringens type D epsilon prototoxin. Animals were killed, 1 h to 14 d postinjection, by perfusion fixation under general anaesthesia. VCO was d
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Toxin-Induced Vasogenic Cerebral Oedema in a Rat Model M. N. Ghabrielt, c. Zhut, P. L. Reilly2, P. c. Blumbergs3.4, J. Manavis4 , and J. W. Finnie4 1 Department
of Anatomical Sciences, University of Adelaide, Australia of Neurosurgery, University of Adelaide, Australia 3 Department of Pathology, University of Adelaide, Australia 4 Institute of Medical and Veterinary Science, Adelaide, Australia
2 Department
Summary Vasogenic cerebral oedema (VeO) was induced in Hooded Wistar rats by intraperitoneal injection of Clostridium perfringens type D epsilon prototoxin. Animals were killed, I h to 14 d postinjection, by perfusion fixation under general anaesthesia. veo was detected by the presence of endogenous albumin in the brain, visualised by immunocytochemistry. As early as I h postinjection, albumin was detected in the walls of cerebral microvessels. Maximal diffuse leakage within the neural parenchyma was seen at 24 and 48 h and immunoreactivity was still present at 4 d. At 7 d only few foci were seen, and at 14 d albumin distribution was similar to that in controls. Ultrastructural assessment of the microvessels showed swelling of many astrocytic processes and abnormalities of the endothelial cells varying from swelling with loss of cytoplasmic organelles to cells showing increased electron density. Immunostaining for the endothelial barrier antigen (EBA) showed strongly immunoreactive vessels throughout normal brains. Experimental animals showed partial reduction in EBA expression, most evident at 24 and 48 h, with gradual recovery to normal by 14 d. The exact role that EBA plays in the intact BBB remains obscure.
Keywords: Blood-brain barrier; cerebral oedema; albumin; endothelial barrier antigen.
Introduction Experimental evidence supports a causal relationship between blood-brain barrier (BBB) changes and the ensuing neuronal structural and functional perturbation in brain pathology. Human vasogenic cerebral oedema (VCO) secondary to breakdown of the BBB is believed to contribute to the morbidity and mortality resulting from head injury [10]. VCO may produce secondary insult in the brain by interfering with the microcirculation and by raising the intracranial pressure. The leakage of plasma proteins in the oedema fluid and the accumulation of neurotoxic substances
such as glutamate may also contribute to the secondary insult [10]. The endothelial barrier antigen (EBA), a protein triplet of 30, 25 and 23.5 kDa, is specifically expressed by rat CNS endothelial cells (ECs) which possess barrier function [7, 11, 12]. A monoclonal antibody (anti-EBA) has been used to probe the distribution of the protein in the rat brain. In diseases associated with alteration in BBB permeability, the expression ofEBA correlated with the state of the disease. In experimental allergic encephalomyelitis (EAE), anti-EBA labeling was abolished in brain vessels surrounded by inflammatory cells and in vessels located in residual lesions, but returned to normal levels after recovery from the acute phase [13]. In stab-wound of the brain
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