ENDOGENOUS BDNF PROTEIN IS INCREASED IN ADULT FLAT HIPPOCAMPUS AFTER A KAINIC ACID-INDUCED EXCITOTOXIC INSULT BUT EXOGENOUS BDNF IS NOT NEUROPROTECTIVE

Systemic administration of the excitotoxin kainic acid to adult rats r esults in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal. loss, brain-derive d neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specif ic areas of the hippocampus, reaching maximal levels 24 h after-the in sult. BDNF protein levels in the hippocampus increase in direct relati on to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length Trk B protein were unchanged, whereas leve ls of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially be neficial. to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal deat h caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyra midal neurons. Although there was a trend toward sparing of CA1 pyrami dal neurons on the side infused with BDNF; this was not significant. I n the same paradigm, infusion of exogenous NT-3 had no effect. (C) 199 8 Academic Press.