Department of Psychology and Program in Neuroscience, Texas Christian University, Forth Worth, TX 76129, USA.
Restor Neurol Neurosci. 1997 Jan 1;11(1):71-82. doi: 10.3233/RNN-1997-111208.
Following brain injury there is an excessive release of glutamate, a reduction in levels of cellular Mg+ +, and the generation of oxygen free radicals. These processes may contribute to the severity of the behavioral impairments seen following brain injury by leading to secondary neuronal degeneration. The present experiment investigates the relative effects of three drugs (MK-801, an NMDA antagonist; magnesium chloride, an NMDA antagonist; and N-tert-butyl-α-phenylnitrone (PBN), an anti-oxidant and free radical scavenger) which disrupt different aspects of the pathophysiological process, in reducing these impairments. Direct comparisons of these drugs may determine if one treatment is more effective than another, or if one is detrimental. In addition, the effects of combination treatments including PBN and MK-801 or MgCl2 were examined. These combination treatment were aimed at the possibility of potentiating the beneficial effects observed after administration of these agents alone. Rats received unilateral electrolytic lesions of the somatic sensorimotor cortex followed by a regimen of MK-801 (1 mg/kg), MgCl2 (1 mmol/kg), PBN (100 mg/kg), MK-801 + PBN (1 mg/kg, 100 mg/kg), MgCl2 + PBN (1 mmol/kg, 100 mg/kg), or saline (1 ml/kg) beginning 15 min following injury. Rats were tested on several sensorimotor tasks (i.e. forelimb placing and foot-fault) for 43 days following the cortical lesions. Rats receiving any of the single or combination drug treatments showed a significant facilitation of recovery on the sensorimotor tasks compared to saline control rats. On one behavioral test (i.e. foot-fault) there was a significant further enhancement of the recovery by combination treatments compared to the single treatment groups. These data are consistent with the idea that excessive release of glutamate, reduction in Mg+ + levels, and free radical generation contribute to the severity of the behavioral impairments following cortical injury, and that arresting these processes results in a facilitation of behavioral recovery. Anatomical analysis showed that all drug treatments decreased the amount of atrophy seen in the ipsilateral striatum.
脑损伤后谷氨酸大量释放，细胞内镁离子水平降低，氧自由基生成。这些过程可能导致继发性神经元变性，从而加重脑损伤后的行为障碍。本实验研究了三种药物（MK-801，NMDA 拮抗剂；氯化镁，NMDA 拮抗剂；N-叔丁基-α-苯基硝酮（PBN），抗氧化剂和自由基清除剂）的相对作用，这些药物可破坏病理生理过程的不同方面，从而减轻这些损伤。直接比较这些药物可以确定一种治疗方法是否比另一种更有效，或者一种是否有害。此外，还检查了包括 PBN 和 MK-801 或 MgCl2 在内的联合治疗的效果。这些联合治疗旨在增强单独使用这些药物后观察到的有益效果的可能性。大鼠接受单侧体感运动皮层电解损伤，然后接受 MK-801（1mg/kg）、MgCl2（1mmol/kg）、PBN（100mg/kg）、MK-801+PBN（1mg/kg，100mg/kg）、MgCl2+PBN（1mmol/kg，100mg/kg）或生理盐水（1ml/kg）治疗，损伤后 15 分钟开始治疗。大鼠在皮层损伤后 43 天接受多项感觉运动任务（即前肢放置和足部失误）测试。与生理盐水对照组相比，接受任何单一或联合药物治疗的大鼠在感觉运动任务上的恢复明显得到促进。在一项行为测试（即足部失误）中，与单一治疗组相比，联合治疗组的恢复进一步显著增强。这些数据与以下观点一致：谷氨酸过度释放、镁离子水平降低和自由基生成导致皮质损伤后行为障碍的严重程度，阻止这些过程可促进行为恢复。解剖分析显示，所有药物治疗均减少了同侧纹状体萎缩的程度。
