Smad3 deficiency increases cortical and hippocampal neuronal loss following traumatic brain injury

Sonia Villapol, Yu Wang, Matthew Adams, Aviva J Symes

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Transforming growth factor-β (TGF-β) signaling is involved in pathological processes following brain injury. TGF-β signaling through Smad3 contributes significantly to the immune response and glial scar formation after brain injury. However, TGF-β is also neuroprotective, suggesting that Smad3 signaling may also be involved in neuroprotection after injury. We found expression of the TGF-β type II receptor (TβRII) and Smad3 protein to be strongly and rapidly induced in neurons in the ipsilateral cortex and CA1 region of the hippocampus after stab wound injury. In contrast, astrocytic expression of TβRII and Smad3 was induced more slowly. Comparison of the response of wild-type and Smad3 null mice to cortical stab wound injury showed a more pronounced loss of neuronal viability in Smad3 null mice. Neuronal density was more strongly reduced in Smad3 null mice than in wild-type mice at 1 and 3days post lesion in both the ipsilateral cortex and hippocampal CA1 region. Fluoro-Jade B, TUNEL staining, and cleaved caspase-3 staining also demonstrated increased neuronal degeneration at early time points after injury in the ipsilateral hemisphere in Smad3 null mice. Taken together, our results suggest that TGF-β cytokine family signaling through Smad3 protects neurons in the damaged cortex and hippocampus at early time points after injury.

Original languageEnglish (US)
Pages (from-to)353-65
Number of pages13
JournalExperimental Neurology
StatePublished - Dec 2013


  • Animals
  • Brain Injuries
  • Cerebral Cortex
  • Fluorescent Antibody Technique
  • Hippocampus
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Degeneration
  • Neurons
  • Protein-Serine-Threonine Kinases
  • Receptors, Transforming Growth Factor beta
  • Signal Transduction
  • Smad3 Protein
  • Journal Article
  • Research Support, Non-U.S. Gov't


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