Conditional overexpression of insulin-like growth factor-1 enhances hippocampal neurogenesis and restores immature neuron dendritic processes after traumatic brain injury

J Neuropathol Exp Neurol. 2014 Aug;73(8):734-46. doi: 10.1097/NEN.0000000000000092.


Traumatic brain injury (TBI) is associated with neuronal damage or neuronal death in the hippocampus, a region critical for cognitive function. Immature neurons within the hippocampal neurogenic niche are particularly susceptible to TBI. Therapeutic strategies that protect immature hippocampal neurons or enhance posttraumatic neurogenesis may be advantageous for promoting functional recovery after TBI. Insulin-like growth factor-1 (IGF-1) promotes neurogenesis in the adult brain, but its effects on neurogenesis after TBI are unknown. We used an astrocyte-specific conditional IGF-1-overexpressing mouse model to supplement IGF-1 in regions of neuronal damage and reactive astrocytosis after controlled cortical impact injury. Although early loss of immature neurons was not significantly attenuated, overexpression of IGF-1 resulted in a marked increase in immature neuron density in the subgranular zone at 10 days after injury. This delayed increase seemed to be driven by enhanced neuron differentiation rather than by increased cellular proliferation. In wild-type mice, dendrites of immature neurons exhibited significant decreases in total length and number of bifurcations at 10 days after injury versus neurons in sham-injured mice. In contrast, the morphology of immature neuron dendrites in brain-injured IGF-1-overexpressing mice was equivalent to that in sham controls. These data provide compelling evidence that IGF-1 promotes neurogenesis after TBI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain Injuries / pathology*
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation
  • Dendrites / pathology*
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Gene Expression Regulation, Developmental
  • Hippocampus / pathology*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis / physiology*
  • Neurons / pathology*
  • Neuropeptides / metabolism
  • Stem Cell Niche / physiology


  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Insulin-Like Growth Factor I
  • Bromodeoxyuridine