RECIPROCAL UP-REGULATION AND DOWN-REGULATION OF BDNF MESSENGER-RNA INTETANUS TOXIN-INDUCED EPILEPTIC FOCUS AND INHIBITORY SURROUND IN CEREBRAL-CORTEX

Chronic focal epilepsy is associated with synaptic plasticity and grow th of new connections. Brain-derived neurotrophic factor (BDNF) is ass ociated with each of these processes in normal brain and shows acute u p-regulation in models of generalized epilepsy. Here, using an experim ental model of focal epilepsy, we show persistent up-regulation of BDN F mRNA, independent of that of other growth factors, in association wi th the development and persistence of chronic seizures. In situ hybrid ization histochemistry revealed that rats perfused within 2-3 days aft er seizure onset had widespread increases in BDNF mRNA levels in the n eocortex. Rats perfused at later times, however, showed focal up-regul ation of BDNF mRNA at the injection site and down-regulation in a surr ounding cortical zone. Nerve growth factor and neurotrophin-3 mRNAs we re not significantly altered. These reciprocal changes in BDNF gene ex pression in the epileptic focus and the cortical surround may contribu te to plastic changes in epileptic neuronal circuits that accompany th e transition from acute to chronic epilepsy. BDNF down-regulation in t he surround is likely to he associated with the inhibitory surround th at hampers seizure spread, but facilitates the persistence of a chroni c epileptic focus.