FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice
Shinichi Yoshimura, … , Xandra O. Breakefield, Michael A. Moskowitz
Shinichi Yoshimura, … , Xandra O. Breakefield, Michael A. Moskowitz
Published October 15, 2003
Citation Information: J Clin Invest. 2003;112(8):1202-1210. https://doi.org/10.1172/JCI16618.
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FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice

Abstract

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. There 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.

Authors

Shinichi Yoshimura, Tetsuyuki Teramoto, Michael J. Whalen, Michael C. Irizarry, Yasushi Takagi, Jianhua Qiu, Jun Harada, Christian Waeber, Xandra O. Breakefield, Michael A. Moskowitz

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Figure 2

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Effect of gene transfer of FGF-2 with HSV-1 amplicon vector on prolifera...
Effect of gene transfer of FGF-2 with HSV-1 amplicon vector on proliferation of progenitor cells in SGZ after CCI. One hour after sham operation (a) or CCI (panels b–d), HSV-1/mFGF-2 vector (d) or empty vector (c) was injected stereotactically into the injured hippocampus of C57BL/6 mice (see Methods). Mice underwent intraperitoneal injection of BrdU at 6, 7, and 8 days or 13, 14, and 15 after CCI and were killed on day 9 or day 16 (the latter not shown). BrdU staining was detected immunohistochemically as described in Figure 1. Robust BrdU labeling was noted in the SGZ of the ipsilateral DG after CCI (b) vs. sham operation (a), and after CCI in mice injected with HSV-1/mFGF-2 (d) vs. control vector (c). Tissue section coordinate, bregma –1.9 mm. Scale bar: 100 μm. (e) Quantification of BrdU-positive cells in SGZ in C57BL/6 mice injected with HSV-1/mFGF-2 or HSV-1/empty. HSV-1/mFGF-2 or HSV-1/empty was injected into injured hippocampus 1 hour after CCI. BrdU was injected at 6, 7, and 8 days, or 13, 14, and 15 days after CCI, and animals killed on day 9 or 16, respectively. Sham-operated mice were injected with BrdU on days 6, 7, and 8, and killed on day 9. After CCI, mice injected with HSV-1/mFGF-2 (black bars) had a greater number of BrdU-positive cells in SGZ on day 9 vs. HSV-1/empty (gray bar) or after CCI only (white bars). †P < 0.05 compared with sham-control. *P < 0.05 compared with HSV-1/empty (n = 6 per group).