Chronic, post-injury administration of D-cycloserine, an NMDA partial agonist, enhances cognitive performance following experimental brain injury.
Chronic, post-injury administration of D-cycloserine, an NMDA partial agonist, enhances cognitive performance following experimental brain injury.
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损伤后长期服用 D-环丝氨酸（一种 NMDA 部分激动剂）可增强实验性脑损伤后的认知能力。
DOI：
10.1016/s0006-8993(96)00940-7
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发表时间：
1996
期刊：
影响因子：
2.9
通讯作者：
Hamm,RJ
中科院分区：
文献类型：
--
作者：
Temple,MD;Hamm,RJ
本研究的目的是确定增强NMDA受体激活对创伤性脑损伤（TBI）产生的认知障碍的影响。具体而言，d-环丝氨酸（DCS），NMDA相关的甘氨酸位点的部分激动剂，作为一个潜在的认知增强剂进行了测试。使用侧向流体冲击TBI（2.8 > 0.10atm）损伤大鼠。在损伤后第1-15天，将动物注射（i. p.）给予溶媒（n = 8）、10 mg/kg（n = 9）或30 mg/kg（n = 8）DCS。使用溶媒（n = 8）或30 mg/kg DCS（n = 8）处理的假损伤动物进行比较。在损伤后第11-15天，使用Morris水迷宫（MWM）评估认知功能。结果表明，与受伤的载体治疗的动物相比，30 mg/kg剂量的DCS显著减轻记忆缺陷（P < 0.01）。分析还揭示，损伤的DCS（30 mg/kg）组的表现与用载体治疗的假损伤动物没有显著差异（P > 0.10）。相比之下，10 mg/kg剂量的DCS在减少损伤诱导的记忆缺陷方面无效。DCS（30 mg/kg）也显著改善假损伤动物的空间记忆（P < 0.05）。总之，慢性损伤后增强NMDA受体是改善TBI相关认知缺陷的有效策略。
The purpose of this study was to determine the effect of augmenting NMDA receptor activation on cognitive deficits produced by traumatic brain injury (TBI). Specifically, d-cycloserine (DCS), a partial agonist of the NMDA-associated glycine site, was tested as a potential cognitive enhancer. Rats were injured using lateral fluid percussion TBI (2.8 > .10 atm). On days 1–15 post-injury, animals were injected (i.p.) with vehicle (n = 8), 10 mg/kg (n = 9), or 30 mg/kg (n = 8) of DCS. Sham-injured animals treated with either vehicle (n = 8) or 30 mg/kg of DCS (n = 8) were used for comparison. On days 11–15 post-injury, cognitive function was assessed using the Morris water maze (MWM[. Results indicate that the 30 mg/kg dose of DCS significantly attenuated memory deficits as compared to injured vehicle-treated animals (P < 0.01). Analysis also revealed that performance of the injured-DCS (30 mg/kg) group was not significantly different from sham-injured animals treated with vehicle (P > 0.10). In contrast, the 10 mg/kg dose of DCS was ineffective in reducing injury-induced memory deficits. DCS (30 mg/kg) also significantly improved the spatial memory of sham-injured animals when compared with sham-injured animals treated with vehicle (P < 0.05). In conclusion, chronic, post-injury enhancement of the NMDA receptor is an effective strategy for ameliorating TBI-associated cognitive deficits.