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

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 GABAA receptor.