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We present a simple in vivo model in which primary astrocyte loss is followed by microvascular damage, using the metabolic toxin 3\u2010chloropropanediol (S\u2010\u03b1\u2010chlorohydrin). This model is uncomplicated by trauma, ischaemia, or primary immune involvement, permitting the study of the role of astrocytes in vascular endothelium integrity, maintenance of the BBB, and neuronal function. Male Fisher F344 rats given 3\u2010chloropropanediol show astrocytic damage and death at 4\u201324 h in symmetrical brainstem and midbrain nuclear lesions, while neurons show morphological changes at 24\u201348 h. Fluorescent 10 kDa dextran tracers show the BBB leaking from 24 h, progressing to petechial haemorrhage after 48\u201372 h, with apparent repair after 6 days. BBB breakdown, but not the earlier astrocytic death, is accompanied by a delayed increase in blood flow in the inferior colliculus. An ED1 inflammatory response develops well after astrocyte loss, suggesting that inflammation may not be a factor in starting BBB breakdown. This model demonstrates that the BBB can self\u2010repair despite the apparent absence of direct astrocytic\u2010endothelial contact. The temporal separation of pathological events allows pharmacological intervention, and the mild reversible ataxia permits long\u2010term survival studies of repair mechanisms. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.10333","type":"journal-article","created":{"date-parts":[[2004,2,10]],"date-time":"2004-02-10T09:00:30Z","timestamp":1076403630000},"page":"325-337","source":"Crossref","is-referenced-by-count":103,"title":["Focal astrocyte loss is followed by microvascular damage, with subsequent repair of the blood\u2010brain barrier in the apparent absence of direct astrocytic contact"],"prefix":"10.1002","volume":"45","author":[{"given":"Colin L.","family":"Willis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Nolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon 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