Diffusion tensor imaging detects axonal injury in a mouse model of repetitive closed-skull traumatic brain injury

Neurosci Lett. 2012 Apr 4;513(2):160-5. doi: 10.1016/j.neulet.2012.02.024. Epub 2012 Feb 17.


Mild traumatic brain injuries (TBI) are common in athletes, military personnel, and the elderly, and increasing evidence indicates that these injuries have long-term health effects. However, the difficulty in detecting these mild injuries in vivo is a significant impediment to understanding the underlying pathology and treating mild TBI. In the following experiments, we present the results of diffusion tensor imaging (DTI) and histological analysis of a model of mild repetitive closed-skull brain injury in mouse. Histological markers used included silver staining and amyloid precursor protein (APP) immunohistochemistry to detect axonal injury, and Iba-1 immunohistochemistry to assess microglial activation. At 24h post-injury, before silver staining or microglial abnormalities were apparent by histology, no significant changes in any of the DTI parameters were observed within white matter. At 7 days post-injury we observed a reduction in axial and mean diffusivity. Relative anisotropy at 7 days correlated strongly with the degree of silver staining. Interestingly, APP was not observed at any timepoint examined. In addition to the white matter alterations, mean diffusivity was elevated in ipsilateral cortex at 24h but returned to sham levels by 7 days. Altogether, this demonstrates that DTI is a sensitive method for detecting axonal injury despite a lack of conventional APP pathology. Further, this reflects a need to better understand the histological basis for DTI signal changes in mild TBI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology*
  • Brain / metabolism
  • Brain / pathology*
  • Brain Injuries / complications*
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Calcium-Binding Proteins / metabolism
  • Diffuse Axonal Injury / diagnosis*
  • Diffuse Axonal Injury / etiology
  • Diffusion Tensor Imaging
  • Disease Models, Animal
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Microglia / metabolism
  • Microglia / pathology
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / pathology
  • Silver Staining


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Microfilament Proteins