Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig

Xiao Han Chen, David F. Meaney, Bai Nan Xu, Masahiro Nonaka, Tracy K. McIntosh, John A. Wolf, Kathryn E. Saatman, Douglas H. Smith

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Although accumulation of neurofilament (NF) proteins in axons has been recognized as a prominent feature of brain trauma, the temporal course of the accumulation of specific NF subtypes has not been well established. In the present study, 17 miniature swine were subjected to nonimpact inertial brain injury. At 3 hours (h), 6 h, 24 h, 3 days, 7 days, and 10 days post-trauma, immunohistochemical analysis was performed to determine axonal accumulation of NF-light (NF-L), the rod and sidearm domains and sidearm phosphorylation states of NF-medium (NF-M), and heavy (NF-H). We found that NF-L accumulation was easily identified in damaged axons by 6 h post-trauma, but NF-M and H accumulation was not clearly visualized until 3 days following injury. In addition, the axonal accumulation of NF-M and H appeared to be primarily comprised of the sidearm domains. While the accumulating NF was found to be predominantly dephosphorylated, we also detected accumulation of phosphorylated NF. Finally, we found that developing axonal pathology may proceed either towards axotomy with discrete terminal bulb formation or towards the development of varicose swellings encompassing long portions of axons. These findings suggest that there is a differential temporal course in NF subtype disassembly, dephosphorylation, and accumulation in axons following initial brain trauma and that these processes occur in morphologically distinct phenotypes of maturing axonal pathology.

Original languageEnglish
Pages (from-to)588-596
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Issue number6
StatePublished - Jun 1999


  • Diffuse axonal injury
  • Inertial brain injury
  • Neurofilament
  • Phosphorylation

ASJC Scopus subject areas

  • General Medicine


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