Hoane M R, Barbay S, Barth T M
Department of Psychology, East Carolina University, Greenville, NC 27858, USA.
Brain Res Bull. 2000 Sep 15;53(2):175-86. doi: 10.1016/s0361-9230(00)00327-0.
Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. Rats were given large unilateral electrolytic lesions of the SMC, administered either the N-methyl-D-aspartate (NMDA) antagonist, MK-801 or saline 16 h after injury, and tested on a battery of behavioral tests. Enduring behavioral deficits were observed, for at least 6 months, on two tests of forelimb placing while transient deficits were observed on the foot-fault and somatosensory neutralization tests. Administration of MK-801 facilitated recovery on the somatosensory neutralization test; however, it did not induce recovery on either forelimb placing test. A second experiment was performed to determine if earlier administration of MK-801, the NMDA antagonist magnesium chloride (MgCl(2)), or the anti-oxidant N-tert-butyl-alpha-phenylnitrone (PBN) could induce behavioral recovery in this chronic model. Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl(2) but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl(2), or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats.
先前的研究利用了一种皮质损伤的损伤模型，该模型会产生短暂的行为障碍，以研究功能恢复过程。为了更好地理解恢复过程，使用一种能产生更严重、持久行为障碍的损伤模型将是有益的。实验1的目的是验证感觉运动皮层（SMC）的大面积损伤，包括喙侧前肢和尾侧前肢区域，是否会产生持久的行为缺陷。给大鼠进行SMC的单侧大面积电解损伤，在损伤后16小时给予N-甲基-D-天冬氨酸（NMDA）拮抗剂MK-801或生理盐水，并在一系列行为测试中进行检测。在两项前肢放置测试中观察到至少6个月的持久行为缺陷，而在足部失误和体感中和测试中观察到短暂缺陷。给予MK-801促进了体感中和测试中的恢复；然而，它在任何一项前肢放置测试中都没有诱导恢复。进行了第二项实验，以确定更早给予MK-801、NMDA拮抗剂氯化镁（MgCl₂）或抗氧化剂N-叔丁基-α-苯基硝酮（PBN）是否能在这个慢性模型中诱导行为恢复。用这些药物治疗在前肢放置测试中诱导了行为恢复，而用生理盐水治疗的大鼠在至少3个月内没有表现出任何行为恢复迹象。纹状体的解剖分析表明，MK-801和MgCl₂而不是PBN减少了损伤诱导的纹状体萎缩程度。这些结果表明，在皮质损伤后不久给予MK-801、MgCl₂或PBN可以诱导功能恢复，而在未治疗的大鼠中原本预期不会恢复。
