Brain-derived neurotrophic factor immunoreactivity in the limbic system ofrats after acute seizures and during spontaneous convulsions: Temporal evolution of changes as compared to neuropeptide Y

Seizures increase the synthesis of brain-derived neurotrophic factor in for ebrain areas, suggesting this neurotrophin has biological actions in epilep tic tissue. The understanding of these actions requires information on the sites and extent of brain-derived neurotrophic factor production in areas i nvolved in seizures onset and their spread. In this study, we investigated by immunocytochemistry the changes in brain-derived neurotrophic factor in the hippocampus, entorhinal and perirhinal cortices of rats at increasing t imes after acute seizures eventually leading to spontaneous convulsions. We also tested the hypothesis that seizure-induced changes in brain-derived n eurotrophic factor induce later modifications in neuropeptide Y expression by comparing, in each instance, their immunoreactive patterns. As early as 100 min after seizure induction, brain-derived neurotrophic actor immunorea ctivity increased in CAI pyramidal and granule neurons and in cells of laye rs II-III of the entorhinal cortex. At later times, immunoreactivity progre ssively decreased in somata while increasing in fibres in the hippocampus, the subicular complex and in specific layers of the entorhinal and perirhin al cortices. Changes in neuropeptide Y immunoreactivity were superimposed u pon and closely followed those of brain-derived neurotrophic factor. One we ek after seizure induction, brain-derived neurotrophic factor and neuropept ide Y immunoreactivities were similar to controls in 50% of rats. In rats e xperiencing spontaneous convulsions, brain-derived neurotrophic factor and neuropeptide Y immunoreactivity was strongly enhanced in fibres in the hipp ocampus/parahippocampal gyrus and in the temporal cortex. In the dentate gy rus, changes in immunoreactivity depended on sprouting of mossy fibres as a ssessed by growth-associated protein-43-immunoreactivity. These modificatio ns were inhibited by repeated anticonvulsant treatment with phenobarbital. The dynamic and temporally-linked alterations in brain-derived neurotrophic factor and neuropeptide Y in brain regions critically involved in epilepto genesis suggest a functional link between these two substances in the regul ation of network excitability. (C) 1999 IBRO. Published by Elsevier Science Ltd.