Aberrant Neurogenesis After Stroke A Retroviral Cell Labeling Study
Aberrant Neurogenesis After Stroke A Retroviral Cell Labeling Study
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DOI：
10.1161/strokeaha.112.660977
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发表时间：
2012-09-01
期刊：
影响因子：
8.3
通讯作者：
Redecker, Christoph
中科院分区：
文献类型：
--
作者：
Niv, Fanny;Keiner, Silke;Redecker, Christoph
背景和目的：成年人齿状回的神经发生是脑可塑性的一种独特形式，在中风后受到强烈刺激。我们调查新的颗粒细胞，这是出生和发展后，缺血insult. Methods，两个完善的模型，这些成年出生的神经元是否正确地整合到预先存在的海马circuitryes. Methods的形态学特性被用来诱导小皮质梗死（phototherapy模型）或大的领土梗死（短暂的大脑中动脉闭塞模型）。在初始损伤后4天，通过海马内注射编码绿色荧光蛋白的逆转录病毒载体标记新的颗粒细胞，并在6周时使用半自动Neurolucida系统和共聚焦激光扫描显微镜对新生神经元进行形态学分析。大脑中动脉闭塞后，也异位细胞的位置。大面积梗死后形态学异常的程度更高，似乎取决于缺血性损伤的严重程度。异常神经元中蘑菇刺比例的增加表明突触整合稳定。然而，中风后产生的颗粒细胞，定期外观也表现出树突状复杂性和脊柱morphology. Conclusions的显著刺激中风后的齿状神经发生与异常整合的神经元，这可能有助于功能障碍的增加率相一致，假设，有利于调节障碍，认知功能障碍，或癫痫的发病机制经常在中风患者中看到。（中风。2012;43：2468-2475）。
Background and Purpose-Adult neurogenesis in the dentate gyrus is a unique form of brain plasticity that is strongly stimulated after stroke. We investigate the morphological properties of new granule cells, which are born and develop after the ischemic insult, and query whether these adult-born neurons properly integrate into the pre-existing hippocampal circuitries.Methods-Two well-established models were used to induce either small cortical infarcts (photothrombosis model) or large territorial infarcts (transient middle cerebral artery occlusion model). New granule cells were labeled 4 days after the initial insult by intrahippocampal injection of a retroviral vector encoding green fluorescent protein and newborn neurons were morphologically analyzed using a semiautomatic Neurolucida system and confocal laser scanning microscopy at 6 weeks.Results-Approximately 5% to 10% of newborn granule cells displayed significant morphological abnormalities comprising additional basal dendrites and, after middle cerebral artery occlusion, also ectopic cell position. The extent of morphological abnormalities was higher after large territorial infarcts and seems to depend on the severity of ischemic damage. An increased portion of mushroom spines in aberrant neurons suggests stable synaptic integration. However, poststroke generated granule cells with regular appearance also demonstrate alterations in dendritic complexity and spine morphology.Conclusions-The remarkable stimulation of dentate neurogenesis after stroke coincides with an increased rate of aberrantly integrated neurons, which may contribute to functional impairments and, hypothetically, favor pathogenesis of adjustment disorders, cognitive deficits, or epilepsy often seen in stroke patients. (Stroke. 2012;43:2468-2475.)