Characterization of cells with proliferative activity after a brain injury
Characterization of cells with proliferative activity after a brain injury
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DOI：
10.1016/j.neuint.2004.12.007
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发表时间：
2005-04-01
影响因子：
4.2
通讯作者：
Wanaka, A
中科院分区：
文献类型：
--
作者：
Tatsumi, K;Haga, S;Wanaka, A
对脑损伤的细胞反应是恢复大脑完整性和功能的重要步骤。活化细胞，如反应性星形胶质细胞、少突胶质细胞前体细胞和小胶质细胞重塑受损组织。为了在空间和时间上表征体内的初始细胞反应，在皮质冷冻损伤后不久（第2天）用BrdU脉冲标记增殖细胞，并通过用抗BrdU抗体和各种细胞标记物的抗体进行双标记来研究它们的命运。冷冻损伤后三天，一个显着比例的BrdU阳性细胞呈阳性NG 2-蛋白聚糖，表明少突胶质细胞祖细胞（OPC）诱导响应损伤。冷冻损伤后1 ~ 2周，OPC数量减少，GFAP/BrdU双阳性细胞逐渐占优势，而具有成熟少突胶质细胞标志物的细胞没有明显增加。在整个研究期间，神经元标记物很少与BrdU免疫反应性共定位。这些发现意味着OPCs易于在损伤部位分化为星形胶质细胞。在该冷冻损伤模型中，甲状腺激素（T4）治疗改变了细胞命运; GFAP/BrdU阳性细胞数量的增加显着减少，并且表现出BrdU免疫反应性的成熟少突胶质细胞（CNE 4，PLP阳性）数量增加。这些发现表明，通过激素或化学治疗对损伤脑中增殖的祖细胞进行修饰可能有利于功能再生。(c)2005爱思唯尔有限公司保留所有权利。
The cellular responses to a brain injury are important steps in restoring the integrity and function of the brain. Proliferating cells, such as reactive astrocytes, oligodendrocyte precursor cells and microglia remodel the injured tissue. To spatially and temporally characterize the initial cellular responses in vivo, proliferating cells were pulse-labeled with BrdU soon after (the 2nd day) a cortical cryo-injury, and their fate was investigated by double labeling with an anti-BrdU antibody and antibodies to various cellular markers. Three days after the cryo-injury, a significant proportion of BrdU-positive cells were positive for NG2-proteoglycan, suggesting that oligodendrocyte progenitors (OPCs) were induced in response to injury. One-two weeks after the cryo-injury, the number of OPC was reduced and GFAP/BrdU double-positive cells, in turn, became dominant, while cells with mature oligodendrocyte markers did not increase significantly. Neuronal markers were rarely colocalized with BrdU immunoreactivity throughout the period studied. These findings imply that OPCs are prone to differentiate to astrocytes in the lesioned site. In this cryo-injury model, treatment with thyroid hormone (T4) altered cell fate; the increase in the number of GFAP/ BrdU-positive cells was significantly diminished, and there was an increased number of mature oligodendrocytes (CNPase, PLP-positive) exhibiting BrdU immunoreactivity. These findings suggest that modification of proliferating progenitors in injured brain by hormonal or chemical treatment might benefit functional regeneration. (c) 2005 Elsevier Ltd. All rights reserved.