Effects of MK-801 and L-NA on the survival and regeneration of axotomized retinal ganglion cells in adult hamsters

Abstract

Objective The present study examined the effects of MK-801,an antagonist against NMDA receptor,and L-NA,an inhibitor of nitric oxide synthase,on the survival and regeneration of axotomized retinal ganglion cells(RGCs) in adult hamsters. Methods This study consisted of two groups.The animals in the survival group survived for 2,7,or 14 days after their left optic nerves(ON) were transected intraorbitally.Animals in the regeneration group survived for 28 days after receiving the left ON transection and peripheral nerve transplantation onto the ocular ON stump.All the experimental animals were treated with daily intraperitoneal injections of MK-801 and/or L-NA one day before ON transection till they were killed. Results No significant difference in the number of surviving RGCs was found between the MK-801-treated and control animals.However,L-NA promoted more RGCs to survive at 2 and 7 day postoperatively when compared with the control animals.More RGCs were detected in animals receiving combined treatment of MK-801/L-NA in comparison to those treated with MK-801 or L-NA only.Similar numbers of regenerating RGCs were encountered among the animals receiving MK-801,L-NA or saline.Conclusion 1^0mg/kg of MK-801 has no promoting effects on the survival of axotomized RGCs,whereas stronger neuroprotective effects can be harvested with combined blockade of NMDA receptor and inhibition of nitric oxide synthesis than with MK-801 or L-NA only. Neither 1^0mg/kg of MK-801 nor 4^5mg/kg of L-NA could enhance the axonal regeneration of axotomized RGCs into a peripheral nerve graft.

研究NMDA受體阻斷劑MK 80 1和一氧化氮合酶抑制劑L NA對成年倉鼠視網膜節細胞 (下稱節細胞 )軸突切斷后存活和再生的影響。 方法 切斷動物左側視神經后分兩組 :存活組存活 2、7或 14d ;再生組視神經眶側斷端同一段坐骨神經吻合后存活 2 8d。所有實驗動物自視神經切斷前 1d開始 ,每日接受腹腔注射MK 80 1和 或L NA直至處死。 結果 存活節細胞均數在MK 80 1組與對照組間無顯著性差異 ,但L NA組在術后 2和 7d節細胞數較對照組顯著增加 ,合用MK 80 1 L NA較單用MK 80 1或L NA使更多節細胞存活。而MK 80 1或L NA對節細胞軸突在周圍神經移植物內的再生均無明顯作用。 結論 1mg/kg劑量的MK 80 1對節細胞的存活無明顯作用 ,但同時阻斷NMDA受體和抑制一氧化氮合酶比單純抑制一氧化氮合酶對節細胞有更強的神經保護作用。 1 0mg/kgMK 80 1或 4 5mg/kgL NA對節細胞軸突的再生無明顯促進作用。