Chronic elevation of brain GABA levels beginning two days after status epilepticus does not prevent epileptogenesis in rats.
Vigabatrin (VGB) treatment is neuroprotective in various models of status epilepticus (SE) and delays the development of kindling via mechanisms that are assumed to relate to the elevation of GABA levels in the brain. Here, we tested the hypothesis that a chronic elevation of brain GABA levels obtained by VGB treatment prevents the development of spontaneous seizures (i.e. epilepsy) following SE in rats. Self-sustained SE (SSSE) was induced by stimulating the lateral nucleus of the amygdala. Two days later, chronic VGB (75 mg/kg/day) or saline treatment was started via subcutaneous osmotic minipumps. The development of spontaneous seizures was monitored once a week (24 h at a time) using video-EEG recording. Rats were perfused for histology either at the end of the 10-week drug treatment, or later at the end of an 8-week drug-free follow-up period. Before perfusion for histology, spatial learning and memory perform was tested in the Morris water-maze. Spontaneous seizures were observed in 55% (6/11) of the saline-treated and 73% (8/11) of the VGB-treated rats during the 10-week treatment period. Seizure frequency, severity, and duration were similar in VGB-treated rats and controls during and after the drug-treatment period. VGB treatment did not decrease neuronal damage in various temporal lobe regions or mossy fiber sprouting. VGB treatment also did not attenuate spatial learning or memory impairments. These findings indicate that the augmentation of GABAergic neurotransmission by VGB does not prevent the development of epilepsy when treatment is started 2 days after SE.
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.
T
T
Halonen
J
J
Nissinen
A
A
Pitkänen
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004569:Electroencephalography; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010640:Phenothiazines / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013004:Somatostatin / Q000032:analysis; D013226:Status Epilepticus / Q000473:pathology / Q000503:physiopathology*; D013550:Swimming; D013997:Time Factors; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D010640:Phenothiazines; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; C009469:thionine