CELLULAR HYBRIDIZAITON FOR BDNF, TRKB, AND NGF MESSENGER-RNAS AND BDNF-IMMUNOREACTIVITY IN RAT FOREBRAIN AFTER PILOCARPINE-INDUCED STATUS EPILEPTICUS

The messenger RNAs (mRNAs) for the neurotrophins, brain-derived neurot rophic factor (BDNF), and nerve growth factor (NGF), are upregulated d uring epileptic seizure activity, as visualized by in situ hybridizati on techniques. Neurotrophins might be protective against excitotoxic c ell stress, and the upregulation during seizures might provide such ce ll protection. In this study, a high dose of pilocarpine (300 mg/kg) w as used to induce long-lasting, limbic motor status epilepticus and a selective pattern of brain damage. The regulation of BDNF, trkB, and N GF mRNA was studied by in situ hybridization at 1, 3, 6, and 24 h afte r induction of limbic motor status epilepticus. BDNF immunoreactivity was examined with an anti-peptide antibody and the neuropathological p rocess studied in parallel. BDNF mRNA increased in hippocampus, neocor tex, piriform cortex, striatum, and thalamus with a maximum at 3-6 h. Hybridization levels increased earlier in the resistant granule and CA 1 cells as compared to the vulnerable CA3 neurons. BDNF immunoreactivi ty was elevated in den tate gyrus at 3-6 h. trkB mRNA increased in the entire hippocampus. NGF mRNA in hippocampus appeared in dentate gyrus at 3-6 h and declined in hilar neurons at 6-24 h. Cell damage was fou nd in the CA3 area, entire basal cortex, and layers II/III of neocorte x. Endogenous neurotrophins are upregulated during status epilepticus caused by pilocarpine, which is related to the coupling between neuron al excitation and trophic factor expression. This upregulation of neur otrophic factors may serve endogenous protective effects; however, the excessive levels of neuronal hyperexcitation resulting from pilocarpi ne seizures lead to cell damage which cannot be prevented by endogenou s neurotrophins.