Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats.

Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats.
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DOI:
10.3389/fnins.2016.00467
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发表时间:
2016
影响因子:
4.3
通讯作者:
Kartje GL
Kartje GL
中科院分区:
医学2区
文献类型:
--
作者:
Shepherd DJ;Tsai SY;O'Brien TE;Farrer RG;Kartje GL

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缺血性中风是成人残疾的主要原因,包括认知障碍。我们的实验室先前已经表明,使用针对神经突生长抑制蛋白Nogo-A的功能阻断抗体治疗可促进成年和老年大鼠中风后的功能恢复,包括增强空间记忆能力,海马体对此至关重要。由于空间记忆与海马神经发生有关,我们研究了抗Nogo-A治疗是否增加卒中后海马神经发生。使成年大鼠经受永久性大脑中动脉闭塞,1周后接着进行2周抗体处理。在治疗结束时定量齿状回中的细胞增殖,并在中风后8周确定新生神经元的数量。用抗Nogo-A和对照抗体治疗刺激齿状颗粒细胞层中新的小胶质细胞/巨噬细胞的积累,但两种治疗都没有增加细胞增殖或高于仅中风水平的新生神经元的数量。这些结果表明,抗Nogo-A免疫治疗不会增加卒中后海马神经发生。
Ischemic stroke is a leading cause of adult disability, including cognitive impairment. Our laboratory has previously shown that treatment with function-blocking antibodies against the neurite growth inhibitory protein Nogo-A promotes functional recovery after stroke in adult and aged rats, including enhancing spatial memory performance, for which the hippocampus is critically important. Since spatial memory has been linked to hippocampal neurogenesis, we investigated whether anti-Nogo-A treatment increases hippocampal neurogenesis after stroke. Adult rats were subject to permanent middle cerebral artery occlusion followed 1 week later by 2 weeks of antibody treatment. Cellular proliferation in the dentate gyrus was quantified at the end of treatment, and the number of newborn neurons was determined at 8 weeks post-stroke. Treatment with both anti-Nogo-A and control antibodies stimulated the accumulation of new microglia/macrophages in the dentate granule cell layer, but neither treatment increased cellular proliferation or the number of newborn neurons above stroke-only levels. These results suggest that anti-Nogo-A immunotherapy does not increase post-stroke hippocampal neurogenesis.
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