Adrenalectomy‐induced cell death in the dentate gyrus: Further characterisation using TUNEL and effects of the Ginkgo bilobaextract, EGb 761, and ginkgolide B

This study investigated the potential neuroprotective effects of the Ginkgo bilobaextract, EGb‐761, and ginkgolide B, on adrenalectomy (ADX)‐induced cell death in the dentate gyrus (DG). Adrenalectomised, sham surgery‐treated, and naive controls received either EGb‐761 (25, 50, or 100 mg/kg), 0.9% saline vehicle control, ginkgolide B (10 or 25 mg/kg), or a polyethylene glycol vehicle control, i.p, daily for 6 days postsurgery. Cell death in the DG was determined by in situ labelling of DNA fragments, using the TUNEL method; sections were counterstained with hematoxylin. Radioimmunoassay was used to confirm a decrease in plasma corticosterone (CORT) after ADX. TUNEL‐positive granule cells were observed in the DG at 1 week, but not at 24 h, post‐ADX. The rate of granule cell death at this time was highest in the suprapyramidal blade and increased in a crest tip and a rostrotemporal gradient. Whereas CORT replacement completely prevented the occurrence of TUNEL‐positive granule cells, EGb‐761 and ginkgolide B did not, at any of the doses used. These results suggest that these drugs may not have substantial neuroprotective effects in the ADX model of neurodegeneration. Hippocampus 2003;13:212–225. © 2003 Wiley‐Liss, Inc.