We have examined the effect of lateral cortical impact injury on the levels of axonal
cytoskeletal proteins in adult rats.
Traumatic brain injury (TBI) causes a significant decrease in the
protein levels of two prominent neurofilament (NF)
proteins,
NF68 and NF200. We employed quantitative immunoreactivity measurements on Western blots to examine
NF68 and NF200 levels in homogenates of hippocampal and cortical tissue taken at several intervals postinjury.
Sham injury had no effect on NF
protein levels. However, injury was associated with a significant loss of
NF68, restricted to the cortex ipsilateral to the injury site.
NF68 loss was detectable as early as 3 h and lasted at least 2 weeks postinjury. Similarly, TBI induced a decrease in NF200
protein, although losses were observed both ipsilateral and contralateral to the injury site. No loss of
NF68 or NF200
protein was detected in hippocampal samples obtained from the same injured animals. An increase in the presence of lower molecular weight (MW)
NF68 immunopositive bands was associated with the decrease of
NF68 in the ipsilateral cortex. This
NF68 antigenicity pattern suggests the production of
NF68 breakdown products caused by the pathologic activation of neuronal
proteases, such as
calpain. Putative
NF68 breakdown products increase significantly until 1 day postinjury, suggesting that NF degradation may be ongoing until that time and indicating that a potential therapeutic window may exist within the first 24 h postinjury. In summary, these data identify specific biochemical alterations of the neuronal cytoskeleton following TBI and lay a foundation for further investigation of postinjury cytoskeletal changes in neuronal processes.