title: Different neuroprotection and therapeutic time windows by two specific diazepam regimens on retinal ganglion cells after optic nerve transection in adult rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Qian
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Feng
authors.forename: Ming-Mei
authors.initials: MM
authors.lastname: Wu
authors.forename: An-An
authors.initials: AA
authors.lastname: Yang
authors.forename: Xi-Ying
authors.initials: XY
authors.lastname: Jiao
authors.forename: Si-Wei
authors.initials: SW
authors.lastname: You
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
mesh_terms: D000375:Aging; D000818:Animals; D019771:Axotomy / Q000009:adverse effects; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use*; D005260:Female; D007274:Injections, Intraperitoneal / Q000379:methods; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020221:Optic Nerve Injuries / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D003975:Diazepam