Selective death of newborn neurons in hippocampal dentate gyrus following moderate experimental traumatic brain injury.
Selective death of newborn neurons in hippocampal dentate gyrus following moderate experimental traumatic brain injury.
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DOI：
10.1002/jnr.21677
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发表时间：
2008-08-01
影响因子：
4.2
通讯作者：
Chen, Jinhui
中科院分区：
文献类型：
--
作者：
Gao, Xiang;Deng-Bryant, Ying;Cho, Wongil;Carrico, Kimberly M.;Hall, Edward D.;Chen, Jinhui
记忆障碍是创伤性脑损伤（TBI）后最重要的残留缺陷之一，也是患者及其亲属最常见的主诉之一。据报道，海马体特别容易受到TBI的影响，这导致海马体依赖性认知障碍。海马体中有不同的区域，每个区域由不同的细胞类型组成，这些细胞类型可能对TBI有不同的反应。然而，区域和细胞类型特异性神经元死亡TBI后没有得到很好的描述。在这里，我们研究了退化神经元的分布在小鼠大脑的海马控制皮质的影响（CCI），发现大多数观察到的退化神经元在中度（0.5毫米皮质变形）CCI-TBI后的齿状回。相反，在门部仅观察到少数变性神经元，并且在CA 3或CA 1区域未观察到任何变性神经元。在齿状回变性细胞中，约80%位于内侧颗粒神经元层。细胞类型特异性标记物分析显示，内颗粒神经元层中的大多数退化神经元是新生的未成熟神经元。进一步的定量分析表明，与对侧相比，同侧大脑半球齿状回新生的未成熟神经元数量显著减少。总的来说，我们的数据表明，选择性死亡的新生未成熟的神经元在海马齿状回中度损伤与CCI小鼠。新生未成熟齿状核神经元的这种选择性脆弱性可能导致TBI后学习和记忆的持续损害，并为神经保护治疗策略提供了一个创新的靶点。
Memory impairment is one of the most significant residual deficits following traumatic brain injury (TBI) and is among the most frequent complaints heard from patients and their relatives. It has been reported that the hippocampus is particularly vulnerable to TBI, which results in hippocampus-dependent cognitive impairment. There are different regions in the hippocampus, and each region is composed of different cell types, which might respond differently to TBI. However, regional and cell type-specific neuronal death following TBI is not well described. Here, we examined the distribution of degenerating neurons in the hippocampus of the mouse brain following controlled cortical impact (CCI) and found that the majority of degenerating neurons observed were in the dentate gyrus after moderate (0.5 mm cortical deformation) CCI-TBI. In contrast, there were only a few degenerating neurons observed in the hilus, and we did not observe any degenerating neurons in the CA3 or CA1 regions. Among those degenerating cells in the dentate gyrus, about 80% of them were found in the inner granular neuron layer. Analysis with cell type-specific markers showed that most of the degenerating neurons in the inner granular neuron layer are newborn immature neurons. Further quantitative analysis shows that the number of newborn immature neurons in the dentate gyrus is dramatically decreased in the ipsilateral hemisphere compared with the contralateral side. Collectively, our data demonstrate the selective death of newborn immature neurons in the hippocampal dentate gyrus following moderate injury with CCI in mice. This selective vulnerability of newborn immature dentate neurons may contribute to the persistent impairment of learning and memory post-TBI and provide an innovative target for neuroprotective treatment strategies.
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