Different neuroprotection and therapeutic time windows by two specific diazepam regimens on retinal ganglion cells after optic nerve transection in adult rats

Abstract

Purpose: To compare neuroprotection and therapeutic time windows of two diazepam regimens on retinal ganglion cells (RGCs) after rat optic nerve transection (ONT). Methods: Adult rats received initial intraperitoneal diazepam injections 30 minutes before left ONT, followed by daily diazepam (Regimen-A) or every 8 hours for 3 days (Regimen-B) until they were killed at Day 7 or 14. Initial diazepam in Regimen-A and Regimen-B was delayed to 3, 6, 7, 9, 10, 12 and 6, 7, 8, 9, 10, 12 hours after ONT and these animals survived for 7 days. The effect of daily combinational uses of diazepam and bicuculline was assayed at 7 days. Results: Regimen-A induced higher RGC densities than those in control and Regimen-B groups at Day 7, but lower density than Regimen-B did at Day 14. When initial diazepam was delayed beyond 6 or 8 hours after ONT with Regimen-A and Regimen-B, the promoting effects of diazepam on RGC densities disappeared. Bicuculline completely inhibited the protection of diazepam. Conclusions: Prolonged neuroprotection on RGCs at Day 14 and extended therapeutic time window for 8 hours can be achieved by Regimen-B, while Regimen-A induces a stronger neuroprotection at Day 7. Diazepam neuroprotection is mediated through GABA_A receptor.