Neuroscience Program, Loyola University Chicago, Maywood, IL 60153, USA.
Behav Brain Res. 2010 Apr 2;208(2):415-24. doi: 10.1016/j.bbr.2009.12.015. Epub 2009 Dec 24.
We have previously shown that immunotherapy directed against the protein Nogo-A leads to recovery on a skilled forelimb reaching task in rats after sensorimotor cortex stroke, which correlated with axonal and dendritic plasticity. Here we investigated anti-Nogo-A immunotherapy as an intervention to improve performance on a spatial memory task in aged rats after stroke, and whether cognitive recovery was correlated with structural plasticity. Aged rats underwent a unilateral distal permanent middle cerebral artery occlusion and one week later were treated with an anti-Nogo-A or control antibody. Nine weeks post-stroke, treated rats and normal aged rats were tested on the Morris water maze task. Following testing rats were sacrificed and brains processed for the Golgi-Cox method. Hippocampal CA3 and CA1 pyramidal and dentate gyrus granule cells were examined for dendritic length and number of branch segments, and CA3 and CA1 pyramidal cells were examined for spine density and morphology. Anti-Nogo-A immunotherapy given one week following stroke in aged rats improved performance on the reference memory portion of the Morris water maze task. However, this improved performance was not correlated with structural changes in the hippocampal neurons examined. Our finding of improved performance on the Morris water maze in aged rats after stroke and treatment with anti-Nogo-A immunotherapy demonstrates the promising therapeutic potential for anti-Nogo-A immunotherapy to treat cognitive deficits after stroke. The identification of sites of axonal and dendritic plasticity in the aged brain after stroke and treatment with anti-Nogo-A immunotherapy is still under investigation.
我们之前已经证明，针对 Nogo-A 蛋白的免疫疗法可导致大脑感觉运动皮层卒中后的大鼠在熟练的前肢伸展任务中恢复，这与轴突和树突的可塑性相关。在这里，我们研究了抗 Nogo-A 免疫疗法作为一种干预措施，以改善卒中后老年大鼠在空间记忆任务中的表现，以及认知恢复是否与结构可塑性相关。老年大鼠接受单侧远端永久性大脑中动脉闭塞，一周后接受抗 Nogo-A 或对照抗体治疗。卒中后 9 周，治疗组大鼠和正常老年大鼠接受 Morris 水迷宫任务测试。测试后，处死大鼠并进行 Golgi-Cox 方法处理。检查海马 CA3 和 CA1 锥体和齿状回颗粒细胞的树突长度和分支段数，检查 CA3 和 CA1 锥体细胞的棘密度和形态。卒中后一周给予老年大鼠抗 Nogo-A 免疫疗法可改善 Morris 水迷宫任务的参考记忆部分的表现。然而，这种改善的表现与所检查的海马神经元的结构变化无关。我们发现卒中后老年大鼠经抗 Nogo-A 免疫疗法治疗后在 Morris 水迷宫上的表现得到改善，这表明抗 Nogo-A 免疫疗法具有治疗卒中后认知缺陷的巨大治疗潜力。卒中后抗 Nogo-A 免疫疗法对老年大脑中的轴突和树突可塑性的研究仍在进行中。
