title: MRI characterisation of a novel rat model of focal astrocyte loss.
abstract: Blood-brain barrier (BBB) integrity is lost in several neurological conditions in which astrocytes are damaged. We studied 3-chloropropanediol-induced focal lesions, a toxicant that induces early astrocytic (but not neuronal) death followed by BBB leakage. T2-weighted images illustrate regional selectivity of the lesions, affected areas including the inferior colliculi and red nuclei. Gd-DTPA intensity quantified the degree of vascular leakage in the lesioned areas. MRI intensity in lesioned areas peaked at 2 days, correlating with BBB breakdown, and diminished thereafter, returning to pre-injection levels by 30 days in parallel with the return of astrocytes. T2 measurements were unchanged at 6 h, a time when astrocyte swelling is marked but the vasculature is intact, but increased at 2 days, consistent with cellular damage and BBB leakage. Gd-DTPA enhancement was also greatest at 2 days then decreased over the next 28 days, indicating a tracer-size-dependent rate of BBB repair. A simple model based on experimentally acquired data indicated that the vascular breakdown was the result of leakage of only a small percentage of blood vessels in the affected areas. Loss of astrocytes contributes to barrier loss, and restoration of astrocytes is needed for full barrier recovery.
authors.affiliation: Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
authors.forename: M J W
authors.initials: MJ
authors.lastname: Prior
authors.forename: A M
authors.initials: AM
authors.lastname: Brown
authors.forename: G
authors.initials: G
authors.lastname: Mavroudis
authors.forename: T
authors.initials: T
authors.lastname: Lister
authors.forename: D E
authors.initials: DE
authors.lastname: Ray
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D019786:Gadolinium DTPA; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008571:Men; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012720:Severity of Illness Index; D000517:alpha-Chlorohydrin
chemical_list: D000517:alpha-Chlorohydrin; D019786:Gadolinium DTPA