| First Author | Villapol S | Year | 2013 |
| Journal | Exp Neurol | Volume | 250 |
| Pages | 353-65 | PubMed ID | 24120438 |
| Mgi Jnum | J:206609 | Mgi Id | MGI:5551552 |
| Doi | 10.1016/j.expneurol.2013.10.008 | Citation | Villapol S, et al. (2013) Smad3 deficiency increases cortical and hippocampal neuronal loss following traumatic brain injury. Exp Neurol 250:353-65 |
| abstractText | Transforming growth factor-beta (TGF-beta) signaling is involved in pathological processes following brain injury. TGF-beta signaling through Smad3 contributes significantly to the immune response and glial scar formation after brain injury. However, TGF-beta is also neuroprotective, suggesting that Smad3 signaling may also be involved in neuroprotection after injury. We found expression of the TGF-beta type II receptor (TbetaRII) 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 TbetaRII 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-beta cytokine family signaling through Smad3 protects neurons in the damaged cortex and hippocampus at early time points after injury. |
