FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice
FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice
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DOI：
10.1172/jci200316618
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发表时间：
2003-10-01
影响因子：
15.9
通讯作者：
Moskowitz, MA
中科院分区：
文献类型：
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作者：
Yoshimura, S;Teramoto, T;Moskowitz, MA
我们研究了FGF-2对实验性创伤性脑损伤（TBI）后海马齿状回颗粒细胞层（GCL）神经发生和细胞丢失的调节作用。在经受受控皮质撞击的FGF-2（-/-）和FGF-2（+/+）小鼠中，在创伤后第6 - 8天注射的BrdU标记的分裂细胞的数目在TBI后第9天增加，并且与神经元特异性核抗原共标记的BrdU阳性细胞的数目在第35天显著增加。然而，在损伤的FGF-2（-/-）小鼠中，与FGF-2（+/+）小鼠相比，BrdU阳性细胞和BrdU阳性神经元（第9、35天）较少。FGF-2（-/-）和FGF-2（+/+）小鼠TBI后GCL的体积和GCL神经元的数量也减少，但在35天时FGF-2（-/-）小鼠两者的减少更大。通过脑内注射编码FGF-2的单纯疱疹病毒-1扩增子载体过表达FGF-2显著增加了C57 BL/6小鼠中分裂细胞（第9天）和BrdU阳性神经元（第35天）的数量。此外，GCL体积的减少也减弱。这些结果表明，FGF-2上调神经发生，并保护神经元免受变性后，在成年海马TBI，FGF-2补充通过基因转移可以减少GCL变性后TBI。
We studied the role of FGF-2 on regulation of neurogenesis and cell loss in the granule cell layer (GCL) of the hippocampal dentate gyrus after experimental traumatic brain injury (TBI). in both FGF-2(-/-) and FGF-2(+/+) mice subjected to controlled cortical impact, the number of dividing cells labeled with BrdU, injected on posttrauma days 6 through 8, increased at 9 days after TBI, and the number of BrdU-positive cells colabeled with neuron-specific nuclear antigen significantly increased at 35 days. However, in injured FGF-2(-/-) mice, BrdU-positive cells and BrdU-positive neurons (days 9, 35) were fewer compared with FGF-2(+/+) mice. The re was also a decrease in the volume of the GCL and the number of GCL neurons after TBI in both FGF-2(-/-) and FGF-2(+/+) mice, but the decrease in both was greater in FGF-2(-/-) mice at 35 days. Overexpression of FGF-2 by intracerebral injection of herpes simplex virus-1 amplicon vectors encoding this factor increased numbers of dividing cells (day 9) and BrdU-positive neurons (day 35) significantly in C57BL/6 mice. Furthermore, the decrease in GCL volume was also attenuated. These results suggest that FGF-2 upregulates neurogenesis and protects neurons against degeneration in the adult hippocampus after TBI, and that FGF-2 supplementation via gene transfer can reduce GCL degeneration after TBI.