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·AIM:To investigate whether bis(7)-tacrine,a multifun-ctional drug,inhibits N-methyl-D-aspartate (NMDA)-activated current in retinal ganglion cells(RGC) and provides neuroprotection against retinal cell damage.·METHODS:Purified RGC cultures were obtained from retinas of 1-3 days old Sprague-Dawley(SD) rats,following a two-step immunopanning procedure.After 7 days of cultivation,the inhibition of NMDA-activated current by bis(7)-tacrine was measured by using patch-clamp recording techniques.In animal experiments,RGCs were damaged after intravitreal injection of NMDA (5|ìL,40nmol) in adult rats.Bis(7)-tacrine(0.05,0.1,0.2mg/kg) or memantine(20mg/kg) was intraperitoneal administered to the rats fifteenminutes before intravitreally injection of NMDA.RGC damage was analyzed by histologic techniques,TUNEL and retrograde labeling techniques.·RESULTS:Whole-cell patch-clamp recordings demonstrated that NMDA (30|ìmol/L) resulted in approximately-50 pA inward currents that were blocked by bis(7)-tacrine(1|ìmol/L).Histological examination and retrograde labeling analysis revealed that bis(7)-tacrine induced a significant neuroprotective effect against NMDA-induced cell damage 7 days after NMDA injection.TUNEL staining showed that pretreatment with bis(7)-tacrine was effective in ameliorating NMDA-induced apoptotic cell loss in the retinal ganglion cell layer 18 hours after injection.·CONCLUSION:Bis(7)-tacrine possesses remarkable neur-oprotective activities against retinal excitotoxicity through inhibition of NMDA receptors.·
· AIM: To investigate whether bis (7) -tacrine, a multifun ctional drug, inhibits N-methyl-D-aspartate (NMDA) -activated current in retinal ganglion cells (RGC) and provide neuroprotection against retinal cell damage. : Purified RGC cultures were obtained from retinas of 1-3 days old Sprague-Dawley (SD) rats, following a two-step immunopanning procedure. After 7 days of cultivation, the inhibition of NMDA-activated current by bis (7) -tacrine was measured by using patch-clamp recording techniques. In animal experiments, RGCs were damaged after intravitreal injection of NMDA (5 μL, 40 nmol) in adult rats. Isis (0.05, 0.1, 0.2 mg / kg) or RESULTS: Whole-cell patch-clamp recordings of the NMDA (30 μmol / kg) were intraperitoneal administered to the rats fifteen minutes before intravitreally injection of NMDA. RGC damage was analyzed by histologic techniques, TUNEL and retrograde labeling techniques. / L) resulted in approximately-50 pA inward currents that were blocked by bi Histological examination and retrograde labeling analysis revealed that bis (7) -tacrine induced a significant neuroprotective effect against NMDA-induced cell damage for 7 days after NMDA injection. TUNEL staining showed that pretreatment (7) -tacrine was effective in ameliorating NMDA-induced apoptotic cell loss in the retinal ganglion cell layer for 18 hours after injection · CONCLUSION: Bis (7) -tacrine possesses remarkable neuro- oprotective activities against retinal excitotoxicity through inhibition of NMDA receptors. ·