Mild Traumatic Brain Injury Induces Transient, Sequential Increases in Proliferation, Neuroblasts/Immature Neurons, and Cell Survival: A Time Course Study in the Male Mouse Dentate Gyrus.
Mild Traumatic Brain Injury Induces Transient, Sequential Increases in Proliferation, Neuroblasts/Immature Neurons, and Cell Survival: A Time Course Study in the Male Mouse Dentate Gyrus.
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DOI：
10.3389/fnins.2020.612749
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发表时间：
2020
影响因子：
4.3
通讯作者：
Eisch AJ
中科院分区：
文献类型：
--
作者：
Clark LR;Yun S;Acquah NK;Kumar PL;Metheny HE;Paixao RCC;Cohen AS;Eisch AJ
轻度创伤性脑损伤（mTBI）在世界范围内普遍存在。mTBI可以损害基于海马的功能，例如记忆，并导致齿状回（DG）的网络过度兴奋，齿状回是海马电路的关键入口点。介导mTBI诱导的海马认知和生理功能障碍的一个候选者是DG神经发生过程中损伤诱导的变化。关于TBI如何影响DG神经发生的过程存在相互矛盾的结果;鉴于神经发生过程和损伤后时期都是动态的，并且神经发生的量化在文献中变化很大，这并不奇怪。即使在少数专门关注轻度损伤的TBI研究中，对于mTBI是否以及如何改变DG神经发生的过程也存在分歧。在这里，我们利用了临床相关的啮齿动物模型mTBI（横向液压冲击损伤，LFPI），金标准的标记物和量化的神经发生过程中，和三个时间点损伤后生成一个全面的图片mTBI如何影响成人海马DG神经发生。雄性C57 BL/6 J小鼠（6-8周龄）接受假手术或经由LFPI的mTBI。在短期（损伤后3天，dpi）、中期（7 dpi）和长期（31 dpi）时间点，通过体视学定量DG亚区（颗粒下区[SGZ]、外颗粒细胞层[oGCL]、分子层和门）中的增殖细胞、成神经细胞/未成熟神经元和存活细胞。数据显示mTBI的该模型诱导同侧SGZ/GCL增殖细胞、成神经细胞/未成熟神经元和存活细胞的瞬时、连续增加，这提示mTBI诱导的神经发生。与这些同侧半球的结果相反，LFPI后对侧半球的关键神经源性DG亚区的测量没有增加。我们在这个mTBI模型中的工作与大多数关于其他和更严重的TBI模型的文献一致，表明TBI刺激DG神经发生的过程。然而，由于我们的DG数据在mTBI提供时间，分区域，和神经发生阶段的分辨率，这些数据是重要的考虑方面的功能的重要性TBI诱导的神经发生过程和未来的工作评估的潜力，更换和/或修复DG神经元在脑TBI后。
Mild traumatic brain injuries (mTBIs) are prevalent worldwide. mTBIs can impair hippocampal-based functions such as memory and cause network hyperexcitability of the dentate gyrus (DG), a key entry point to hippocampal circuitry. One candidate for mediating mTBI-induced hippocampal cognitive and physiological dysfunction is injury-induced changes in the process of DG neurogenesis. There are conflicting results on how TBI impacts the process of DG neurogenesis; this is not surprising given that both the neurogenesis process and the post-injury period are dynamic, and that the quantification of neurogenesis varies widely in the literature. Even within the minority of TBI studies focusing specifically on mild injuries, there is disagreement about if and how mTBI changes the process of DG neurogenesis. Here we utilized a clinically relevant rodent model of mTBI (lateral fluid percussion injury, LFPI), gold-standard markers and quantification of the neurogenesis process, and three time points post-injury to generate a comprehensive picture of how mTBI affects adult hippocampal DG neurogenesis. Male C57BL/6J mice (6-8 weeks old) received either sham surgery or mTBI via LFPI. Proliferating cells, neuroblasts/immature neurons, and surviving cells were quantified via stereology in DG subregions (subgranular zone [SGZ], outer granule cell layer [oGCL], molecular layer, and hilus) at short-term (3 days post-injury, dpi), intermediate (7 dpi), and long-term (31 dpi) time points. The data show this model of mTBI induces transient, sequential increases in ipsilateral SGZ/GCL proliferating cells, neuroblasts/immature neurons, and surviving cells which is suggestive of mTBI-induced neurogenesis. In contrast to these ipsilateral hemisphere findings, measures in the contralateral hemisphere were not increased in key neurogenic DG subregions after LFPI. Our work in this mTBI model is in line with most literature on other and more severe models of TBI in showing TBI stimulates the process of DG neurogenesis. However, as our DG data in mTBI provide temporal, subregional, and neurogenesis-stage resolution, these data are important to consider in regard to the functional importance of TBI-induction of the neurogenesis process and future work assessing the potential of replacing and/or repairing DG neurons in the brain after TBI.
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影响因子：
3.6
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