Wright J W, Clemens J A, Panetta J A, Smalstig E B, Weatherly L A, Kramár E A, Pederson E S, Mungall B H, Harding J W
Department of Psychology, Washington State University, Pullman 99164-4820, USA.
Brain Res. 1996 Apr 22;717(1-2):1-11. doi: 10.1016/0006-8993(95)01454-3.
The antioxidant LY231617 has previously been shown to offer significant protection against postischemic cell death in the hippocampus and corpus striatum of rats. The present results extend this observation by demonstrating a concomitant protection against the spatial memory deficits that accompany damage to the hippocampus, as measured by the circular water maze task. These animals were further tested for changes in associative memory by employing a passive avoidance conditioning task. No deficits in passive avoidance conditioning were measured among the 4-vessel occlusion animals treated with LY231617 or vehicle. However, the intracerebroventricular injection of angiotensin IV (Ang IV) immediately prior to foot-shock conditioning improved retention of the conditioned response during the subsequent 2-day period. These results suggest that LY231617 can offer considerable protection against global ischemia-induced cell death in the hippocampus with resulting preservation of spatial memory abilities. In addition, untreated animals that suffered cell losses in the hippocampus remained capable of responding to the facilitory effect of centrally administered Ang IV on a non-spatial memory task. The hypothesized mechanisms of the protection characteristics of LY231617, and the nootropic effect of Ang IV, are discussed.
抗氧化剂LY231617先前已被证明能为大鼠海马体和纹状体的缺血后细胞死亡提供显著保护。目前的结果扩展了这一观察结果，通过循环水迷宫任务测量发现，它还能同时保护免受海马体损伤所伴随的空间记忆缺陷。通过采用被动回避条件反射任务，进一步测试了这些动物联想记忆的变化。在用LY231617或赋形剂处理的四血管闭塞动物中，未测量到被动回避条件反射的缺陷。然而，在足部电击条件反射前立即脑室内注射血管紧张素IV（Ang IV），可在随后的2天内改善条件反应的保持。这些结果表明，LY231617可以为海马体中全脑缺血诱导的细胞死亡提供相当大的保护，从而保留空间记忆能力。此外，海马体中出现细胞损失的未治疗动物，在非空间记忆任务中，仍能够对中枢给予的Ang IV的促进作用作出反应。文中讨论了LY231617保护特性以及Ang IV促智作用的假设机制。
