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.