Traumatic brain injury recapitulates developmental changes of axons

Hailong Song, Chen Chen, Brian Kelley, Alexandra Tomasevich, Hyoungjoo Lee, Jean Pierre Dolle, Jianlin Cheng, Benjamin Garcia, David F. Meaney, Douglas H. Smith

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


During development, half of brain white matter axons are maintained for growth, while the remainder undergo developmental axon degeneration. After traumatic brain injury (TBI), injured axons also appear to follow pathways leading to either degeneration or repair. These observations raise the intriguing, but unexamined possibility that TBI recapitulates developmental axonal programs. Here, we examined axonal changes in the developing brain in young rats and after TBI in adult rat. Multiple shared changes in axonal microtubule (MT) through tubulin post-translational modifications and MT associated proteins (MAPs), tau and MAP6, were found in both development and TBI. Specifically, degenerating axons in both development and TBI underwent phosphorylation of tau and excessive tubulin tyrosination, suggesting MT instability and depolyermization. Conversely, nearby axons without degenerating morphologies, had increased MAP6 expression and maintenance of tubulin acetylation, suggesting enhanced MT stabilization, thereby supporting survival or repair. Quantitative proteomics revealed similar signaling pathways of axon degeneration and growth/repair, including protein clusters and networks. This comparison approach demonstrates how focused evaluation of developmental processes may provide insight into pathways initiated by TBI. In particular, the data suggest that TBI may reawaken dormant axonal programs that direct axons towards either degeneration or growth/repair, supporting further study in this area.

Original languageEnglish
Article number102332
JournalProgress in Neurobiology
StatePublished - Oct 2022


  • Axon
  • Developmental axon degeneration
  • MAP6
  • Tau
  • Traumatic brain injury
  • Tubulin post-translational modifications


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