title: Vigabatrin-induced lesions in the rat brain demonstrated by quantitative magnetic resonance imaging.
abstract: Rats treated with 250 mg/kg/day vigabatrin showed lesions detected by magnetic resonance imaging (MRI) in the cerebellar white matter in vivo. No lesions were seen in any control animal. As well as these visually apparent lesions, quantitative T2 relaxation time measurements showed a 12 ms increase in cerebellar white matter from 66 +/- 4 ms (SD, n = 5) to 78 +/- 2 ms (SD, n = 7). This region, as expected from previous studies, showed microvacuolation on post-mortem pathology. Additionally, significant increases in T2 relaxation times of 4-9 ms were found in the cerebral cortex, thalamus and hippocampus. Microvacuolation was not detected by post-mortem histopathology in the cerebral cortex or hippocampus, however, immunohistochemical staining for glial fibrillary acidic protein and for macrophages (ED1) showed reactive astrocytes (gliosis) and in more severe cases, microglial proliferation in these regions; such changes were also seen in association with the microvacuoles. No T2 increase was found in the cerebellar grey matter or olfactory bulbs. MRI techniques, including T2 relaxometry, are therefore sensitive for detecting vigabatrin-induced changes, including reactive astrocytosis, microglial proliferation and vacuolation in the rat brain. These results suggest that quantitative MRI should be a useful method for evaluating whether vigabatrin has neuropathological effects when given to patients.
authors.affiliation: Institute of Child Health, London, UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Jackson
authors.forename: S R
authors.initials: SR
authors.lastname: Williams
authors.forename: R O
authors.initials: RO
authors.lastname: Weller
authors.forename: N
authors.initials: N
authors.lastname: van Bruggen
authors.forename: N E
authors.initials: NE
authors.lastname: Preece
authors.forename: S C
authors.initials: SC
authors.lastname: Williams
authors.forename: W H
authors.initials: WH
authors.lastname: Butler
authors.forename: J S
authors.initials: JS
authors.lastname: Duncan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D005904:Glial Fibrillary Acidic Protein; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin