Spontaneous limbic seizures after intrahippocampal infusion of brain-derived neurotrophic factor

Experimental Neurology
Helen E ScharfmanS D Croll

Abstract

The results of several studies have contributed to the hypothesis that BDNF promotes seizure activity, particularly in adult hippocampus. To test this hypothesis, BDNF, vehicle (phosphate-buffered saline, PBS), or albumin was infused directly into the hippocampus for 2 weeks using osmotic minipumps. Rats were examined behaviorally, electrophysiologically, and anatomically. An additional group was tested for sensitivity to the convulsant pilocarpine. Spontaneous behavioral seizures were observed in BDNF-infused rats (8/32; 25%) but not in controls (0/20; 0%). In a subset of six animals (three BDNF, three albumin), blind electrophysiological analysis of scalp recordings contralateral to the infused hippocampus demonstrated abnormalities in all BDNF rats; but not controls. Neuronal loss in BDNF-treated rats was not detected relative to PBS- or albumin-treated animals, but immunocytochemical markers showed a pattern of expression in BDNF-treated rats that was similar to rats with experimentally induced seizures. Thus, BDNF-infused rats had increased expression of NPY in hilar neurons of the dentate gyrus relative to control rats. NPY and BDNF expression was increased in the mossy fiber axons of dentate gyrus granule cells relative ...Continue Reading

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