FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice.
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.
Yoshimura
Shinichi
S
Neuroscience Center, Radiology Department, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, Massachusetts, USA.
Teramoto
Tetsuyuki
T
Whalen
Michael J
MJ
Irizarry
Michael C
MC
Takagi
Yasushi
Y
Qiu
Jianhua
J
Harada
Jun
J
Waeber
Christian
C
Breakefield
Xandra O
XO
Moskowitz
Michael A
MA
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D018891:Dentate Gyrus / Q000503:physiopathology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000502:physiology*; D022761:Gene Transfer, Horizontal; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology*; D009474:Neurons / Q000502:physiology*; D014916:Whole-Body Irradiation
D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine