N-methyl-D-aspartate-induced excitotoxicity in adult rat retina is antagonized by single systemic injection of MK-801
N-methyl-D-aspartate-induced excitotoxicity in adult rat retina is antagonized by single systemic injection of MK-801
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DOI：
10.1007/s002210100688
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发表时间：
2001-05-01
影响因子：
2
通讯作者：
Chan, SO
中科院分区：
文献类型：
--
作者：
Sun, Q;Ooi, VEC;Chan, SO
玻璃体内注射N-甲基-D-天冬氨酸（NMDA）对成年大鼠视网膜产生了实质性的损伤，该损伤主要限于视网膜内层，包括神经节细胞层（GCL）、内核层（INL）、内丛状层和外丛状层。全身注射低剂量MK-801（0.5 mg/kg）（一种有效的NMDA受体拮抗剂）可显著降低视网膜损伤。这种神经保护作用是剂量依赖性的，并且当在NMDA损伤前1小时给予拮抗剂时最有效。腹膜内注射0.5 mg/kg MK-801对NMDA诱导的毒性提供了几乎完全的视网膜保护，如DiI填充的视网膜神经节细胞数量、GCL和INL中经历DNA片段化的细胞数量以及视网膜厚度的水肿变化所定量指示的。损伤后给予MK-801仍然能够对视网膜提供有效的神经保护作用，但当NMDA暴露后4 h给予MK-801时，这种保护作用丧失。目前的结果表明MK-801全身应用在保护成年大鼠视网膜免受与NMDA受体过度激活相关的神经系统疾病方面的治疗潜力。
Intravitreal injection of N-methyl-D-aspartate (NMDA) produced a substantial damage to the adult rat retina that was largely restricted to inner retinal layers, including the ganglion cell layer (GCL), inner nuclear layer (INL), inner, and outer plexiform layers. This retinal damage was significantly reduced by a systemic injection of a low dose of MK-801 (0.5 mg/kg), a potent NMDA-receptor antagonist. This neuroprotection was dose dependent and was most effective when the antagonist was given 1 h before NMDA insult. An intraperitoneal injection of 0.5 mg/kg MK-801 provided a virtually complete protection to the retina to the NMDA-induced toxicity, as indicated quantitatively by the number of DiI-filled retinal ganglion cells, the number of cells in the GCL and INL that undergo DNA fragmentation, and the edematous changes in retinal thickness. A post-lesion administration of MK-801 was still able to provide an effective neuroprotective effect to the retina, but this protection was lost when MK-801 was given 4 h after NMDA exposure. The current results indicate a therapeutic potential of systemic application of MK-801 in protecting the adult rat retina From neurologic disorders related to excessive activation of NMDA receptors.