Effects of vigabatrin treatment on status epilepticus-induced neuronal damage and mossy fiber sprouting in the rat hippocampus

Selective neuronal damage and mossy fiber sprouting may underlie epileptoge nesis and spontaneous seizure generation in the epileptic hippocampus. It m ay be beneficial to prevent their development after cerebral insults that a re known to be associated with a high risk of epilepsy later in life in hum ans. In the present study, we investigated whether chronic treatment with a n anticonvulsant, vigabatrin (gamma-vinyl GABA), would prevent the damage t o hilar neurons and the development of mossy fiber sprouting. Vigabatrin tr eatment was started either 1 h, or 2 or 7 days after the beginning of kaini c acid-induced (9 mg/kg, i.p.) status epilepticus and continued via subcuta neous osmotic minipumps for 2 months (75 mg/kg per day). Thereafter, rats w ere perfused for histological analyses. One series of horizontal sections w as stained with thionine to estimate the total number of hilar neurons by u nbiased stereology. One series was prepared for somatostatin immunohistoche mistry and another for Timm histochemistry to detect mossy fiber sprouting. Our data show that vigabatrin treatment did not prevent the decrease in th e total number of hilar cells, nor the decrease in hilar somatostatin-immun oreactive (SOM-ir) neurons when SOM-ir neuronal numbers were averaged from all septotemporal levels. However, when vigabatrin was administered 2 days after the onset of status epilepticus, we found a mild neuroprotective effe ct on SOM-ir neurons in the septal end of the hippocampus (92% SOM-ir neuro ns remaining; P < 0.05 compared to the vehicle group). Vigabatrin did not p revent mossy fiber sprouting regardless of when treatment was started. Rath er, sprouting actually increased in the septal end of the hippocampus when vigabatrin treatment began 1 h after the onset of status epilepticus (P < 0 .05 compared to the vehicle group). Our data show that chronic elevation of brain GABA levels after status epilepticus does not have any substantial e ffects on neuronal loss or mossy fiber sprouting in the rat hippocampus. (C ) 1999 Elsevier Science B.V. All rights reserved.