Reciprocal up- and down-regulation of BDNF mRNA in tetanus toxin- induced epileptic focus and inhibitory surround in cerebral cortex

Chronic focal epilepsy is associated with synaptic plasticity and growth ofnew connections. Brain-derived neurotrophic factor (BDNF) is associatedwith each of these processes in normal brain and shows acute up-regulationin models of generalized epilepsy. Here, using an experimental model offocal epilepsy, we show persistent up-regulation of BDNF mRNA, independentof that of other growth factors, in association with the development andpersistence of chronic seizures. In situ hybridization histochemistryrevealed that rats perfused within 2-3 days after seizure onset hadwidespread increases in BDNF mRNA levels in the neocortex. Rats perfused atlater times, however, showed focal up-regulation of BDNF mRNA at theinjection site and down- regulation in a surrounding cortical zone. Nervegrowth factor and neurotrophin-3 mRNAs were not significantly altered.These reciprocal changes in BDNF gene expression in the epileptic focus andthe cortical surround may contribute to plastic changes in epilepticneuronal circuits that accompany the transition from acute to chronicepilepsy. BDNF down-regulation in the surround is likely to be associatedwith the inhibitory surround that hampers seizure spread, but facilitatesthe persistence of a chronic epileptic focus.