Alterations in hippocampal neurogenesis following traumatic brain injury in mice
Alterations in hippocampal neurogenesis following traumatic brain injury in mice
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DOI：
10.1016/j.expneurol.2006.05.034
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发表时间：
2006-11-01
影响因子：
5.3
通讯作者：
Fike, John R.
中科院分区：
文献类型：
--
作者：
Rola, Radoslaw;Mizumatsu, Shinichiro;Fike, John R.
临床和实验数据表明，创伤性脑损伤（TBI）引起的认知变化通常表现为海马依赖的空间信息处理功能的缺陷。尽管最近的研究表明，海马齿状亚颗粒区（SGZ）神经元前体细胞的变化可能参与了这些影响的潜在机制仍然难以捉摸。在这里，我们通过量化TBI后14天死亡细胞（TUNEL）、增殖细胞（Ki-67）和未成熟神经元（double ecortin, Dex）的数量，评估了单侧皮质控制对2月龄雄性C57BL6小鼠SGZ神经源性细胞群的影响。损伤后6 h出现死亡细胞，24 h达到峰值，14 d恢复到对照水平。除损伤后48小时出现短暂性增加外，所有时间点的同侧和对侧增殖细胞均减少。同时，与同侧对照相比，未成熟神经元减少了84%。在tbi后第一周，对侧dcx阳性细胞数量也减少；14天后恢复到对照水平。为了确定这些变化是否转化为长期影响，在损伤后1周给予BrdU， 3周后评估新生细胞的表型。TBI导致同侧BrdU阳性细胞和新生神经元（BrdU/NeuN）数量减少，对侧无明显变化，而同侧星形胶质细胞（BrdU/GFAP）增加，激活的小胶质细胞（BrdU/CD68）在单侧和对侧均增加。少突胶质细胞（BrdU/NG2）未见差异。综上所述，这些数据表明创伤性脑损伤改变了神经发生和神经胶质瘤发生。这种改变可能在脑外伤引起的认知障碍中起一定作用。(c) 2006爱思唯尔公司版权所有。
Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed the effects of unilateral controlled cortical impact on neurogenic cell populations in the SGZ in 2-month-old male C57BL6 mice by quantifying numbers of dying cells (TUNEL), proliferating cells (Ki-67) and immature neurons (Doublecortin, Dex) up to 14 days after TBI. Dying cells were seen 6 h after injury, peaked at 24 h and returned to control levels at 14 days. Proliferating cells were decreased on the ipsilateral and contralateral sides at all the time points studied except 48 h after injury when a transient increase was seen. Simultaneously, immature neurons were reduced up to 84% relative to controls on the ipsilateral side. In the first week post-TBI, reduced numbers of Dcx-positive cells were also seen in the contralateral side; a return to control levels occurred at 14 days. To determine if these changes translated into longer-term effects, BrdU was administered 1 week post-injury and 3 weeks later the phenotypes of the newly born cells were assessed. TBI induced decreases in the numbers of BrdU-positive cells and new neurons (BrdU/NeuN) on the ipsilateral side without apparent changes on the contralateral side, whereas astrocytes (BrdU/GFAP) were increased on the ipsilateral side and activated microglia (BrdU/CD68) were increased on both ipsi- and contralateral sides. No differences were noted in oligodendrocytes (BrdU/NG2). Taken together, these data demonstrate that TBI alters both neurogenesis and gliogenesis. Such alterations may play a contributory role in TBI-induced cognitive impainnent. (c) 2006 Elsevier Inc. All rights reserved.