Kermer P, Klöcker N, Bähr M
Department of Neurology, University of Tübingen, Germany.
Exp Neurol. 1999 Jul;158(1):202-5. doi: 10.1006/exnr.1999.7094.
There is growing evidence that caspase inhibition exerts neuroprotective effects in various models of neuronal injury in vivo. However, whether caspase inhibition provides long-term neuroprotection is not known yet. In the present study, we therefore investigated the effects of prolonged caspase inhibition on the survival of adult rat retinal ganglion cells (RGCs) following optic nerve (ON) transection. Four weeks following ON transection the number of surviving RGCs in untreated animals declined to 11% of controls. Treatment for the initial 2 weeks with z-DEVD-cmk, an irreversible inhibitor of ced 3-like caspases, increased the number of surviving RGCs 4 weeks postlesion to 24%. Z-DEVD-cmk treatment over the entire experimental period of 4 weeks had no additional effect. Thus, we still found a neuroprotective effect of caspase inhibition on axotomized RGCs after extended survival time. However, in comparison to our recent observations 2 weeks after optic nerve transection, in which z-DEVD-cmk rescued 46% of RGCs (P. Kermer, N. Klöcker, M. Labes, and M. Bähr, 1998, J. Neurosci. 18(12), 4656-4662) the positive effect clearly decreased. In conclusion, our results indicate that the therapeutical approach presented here results in a significant delay of secondary death rather than providing a permanent and complete rescue of axotomized RGCs.
越来越多的证据表明，在各种体内神经元损伤模型中，半胱天冬酶抑制发挥着神经保护作用。然而，半胱天冬酶抑制是否能提供长期神经保护作用尚不清楚。因此，在本研究中，我们调查了延长半胱天冬酶抑制对视神经切断后成年大鼠视网膜神经节细胞（RGCs）存活的影响。视神经切断后四周，未治疗动物中存活的RGCs数量降至对照组的11%。用z-DEVD-cmk（一种不可逆的类ced 3半胱天冬酶抑制剂）进行最初两周的治疗，使损伤后四周存活的RGCs数量增加到24%。在整个4周的实验期内用z-DEVD-cmk治疗没有额外效果。因此，在延长的存活时间后，我们仍然发现半胱天冬酶抑制对轴突切断的RGCs有神经保护作用。然而，与我们最近在视神经切断后两周的观察结果相比，当时z-DEVD-cmk挽救了46%的RGCs（P. Kermer、N. Klöcker、M. Labes和M. Bähr，1998年，《神经科学杂志》18(12)，4656 - 4662），其积极作用明显降低。总之，我们的结果表明，这里提出的治疗方法导致继发性死亡显著延迟，而不是对轴突切断的RGCs提供永久性和完全的挽救。
