Kartje G L, Schulz M K, Lopez-Yunez A, Schnell L, Schwab M E
Neurology Service, Edward Hines Jr Veteran Affairs Hospital, Hines, IL 60141, USA.
Ann Neurol. 1999 Jun;45(6):778-86. doi: 10.1002/1531-8249(199906)45:6<778::aid-ana12>3.0.co;2-b.
After unilateral cortical lesions in neonatal rats, the spared unablated hemisphere is known to demonstrate remarkable neuroanatomical plasticity in corticofugal connectivity. This same type of structural plasticity is not seen after similar lesions in adult rats. One possibility for the lack of such a plastic response in the adult central nervous system may be the presence of myelin-associated neurite growth inhibitory proteins NI-35/NI-250. These proteins have previously been found to play a crucial role in preventing axotomized fibers from regenerating after adult rat spinal cord lesions. The aim of this study was to determine if blocking these inhibitory proteins by the application of the specific monoclonal antibody IN-1 would enhance corticostriatal plasticity from the spared hemisphere after unilateral cortical lesions in adult rats. Six- to 8-week-old Lewis rats underwent unilateral aspiration lesion of the sensorimotor cortex. Animals were immediately treated with either monoclonal antibody IN-1 or a control antibody released from hybridoma cells in Millipore filter capsules. After a survival period of 12 weeks, the opposite sensorimotor cortex was stereotaxically injected with the anterograde tracer biotinylated dextran amine, and biotinylated dextran amine-positive corticostriatal fibers were analyzed. The monoclonal antibody IN-1-treated animals showed an increase in corticostriatal fibers in the dorsolateral striatum contralateral to the injection site compared with control antibody-treated animals or normal controls, indicating a specific sprouting response in the deafferented zone. These results support the idea that through blockade of myelin-associated neurite inhibitory proteins, lesion-induced corticofugal plasticity is possible even in the adult central nervous system.
新生大鼠单侧皮质损伤后，已知未受损的对侧半球在皮质传出连接方面表现出显著的神经解剖可塑性。成年大鼠在类似损伤后则未观察到这种相同类型的结构可塑性。成年中枢神经系统缺乏这种可塑性反应的一种可能性可能是存在髓磷脂相关的神经突生长抑制蛋白NI-35/NI-250。此前已发现这些蛋白在成年大鼠脊髓损伤后阻止轴突切断的纤维再生方面起关键作用。本研究的目的是确定应用特异性单克隆抗体IN-1阻断这些抑制蛋白是否会增强成年大鼠单侧皮质损伤后对侧半球的皮质纹状体可塑性。6至8周龄的Lewis大鼠接受了感觉运动皮质的单侧抽吸损伤。动物立即接受单克隆抗体IN-1或从微孔滤膜胶囊中的杂交瘤细胞释放的对照抗体治疗。在存活12周后，通过立体定位向对侧感觉运动皮质注射顺行示踪剂生物素化葡聚糖胺，并分析生物素化葡聚糖胺阳性的皮质纹状体纤维。与对照抗体治疗的动物或正常对照相比，单克隆抗体IN-1治疗的动物在注射部位对侧的背外侧纹状体中皮质纹状体纤维增加，表明在去传入区有特异性的发芽反应。这些结果支持这样一种观点，即通过阻断髓磷脂相关的神经突抑制蛋白，即使在成年中枢神经系统中，损伤诱导的皮质传出可塑性也是可能的。
