Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive recovery in rats following traumatic brain injury

Exp Neurol. 2009 Mar;216(1):56-65. doi: 10.1016/j.expneurol.2008.11.011. Epub 2008 Nov 27.


Stem/progenitor cells reside throughout the adult CNS and are actively dividing in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. This neurogenic capacity of the SVZ and DG is enhanced following traumatic brain injury (TBI) suggesting that the adult brain has the inherent potential to restore populations lost to injury. This raises the possibility of developing strategies aimed at harnessing the neurogenic capacity of these regions to repair the damaged brain. One strategy is to enhance neurogenesis with mitogenic factors. As basic fibroblast growth factor (bFGF) is a potent stem cell mitogen, we set out to determine if an intraventricular administration of bFGF following TBI could affect the levels of injury-induced neurogenesis in the SVZ and DG, and the degree to which this is associated with cognitive recovery. Specifically, adult rats received a bFGF intraventricular infusion for 7 days immediately following TBI. BrdU was administered to animals daily at 2-7 days post-injury to label cell proliferation. At 1 or 4 weeks post-injury, brain sections were immunostained for BrdU and neuronal or astrocytic markers. We found that injured animals infused with bFGF exhibited significantly enhanced cell proliferation in the SVZ and the DG at 1 week post-TBI as compared to vehicle-infused animals. Moreover, following bFGF infusion, a greater number of the newly generated cells survived to 4 weeks post-injury, with the majority being neurons. Additionally, animals infused with bFGF showed significant cognitive improvement. Collectively, the current findings suggest that bFGF-enhanced neurogenesis contributes to cognitive recovery following TBI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Brain Injuries / physiopathology
  • Bromodeoxyuridine
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Cerebrum / cytology
  • Cerebrum / drug effects
  • Cerebrum / metabolism
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / metabolism
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblast Growth Factor 2 / therapeutic use
  • Injections, Intraventricular
  • Male
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Treatment Outcome


  • Fibroblast Growth Factor 2
  • Bromodeoxyuridine