Abstract
BackgroundDiffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the central fluid percussion injury (cFPI) TAI model in mice, the neuroinflammatory and astroglial response and behavioral changes are unknown.MethodsTwenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric statistics and principal component analysis (MCSF data).ResultsAt all post-injury time points, β-amyloid precursor protein (β-APP) immunoreactivity revealed widespread bilateral axonal injury and IgG immunostaining showed increased blood–brain barrier permeability. Using vimentin and glial fibrillary acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in cortical regions and important white matter tracts peaking at three days post-injury. Only vimentin was increased post-injury in the internal capsule and only GFAP in the thalamus. Compared to sham-injured controls, an increased number of activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3) appearing one day after TAI (P<0.05 for all cell types) was observed in subcortical white matter. In the MCSF, the behavioral patterns including general activity and exploratory behavior differed between cFPI mice and sham-injured controls.ConclusionsTraumatic axonal injury TAI resulted in marked bilateral astroglial and neuroinflammatory responses and complex behavioral changes. The cFPI model in mice appears suitable for the study of injury mechanisms, including neuroinflammation, and the development of treatments targeting TAI.
Highlights
Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality
We show that the central fluid percussion injury (cFPI) model causes a dynamic and widespread, bilateral astroglial and neuroinflammatory response in addition to axonal injury in important white matter tracts
Direct comparisons between the previously published [28] and present data must be made with caution, an identical experimental set-up was used and all behavioral testing was performed by the same investigator. These results argue that the cFPI model induces unique behavioral deficits with a markedly different pattern compared to focal traumatic brain injury (TBI)
Summary
Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. DAI is frequently observed following traffic accidents, sports injuries and falls, and across the entire spectrum of traumatic brain injury (TBI) severity [1,2,3,4]. The morbidity and mortality associated with TBI are closely linked to the extent of axonal injury in subcortical, central and brainstem white matter tracts. A major consequence of DAI is unconsciousness and persistent vegetative state that can be observed up to many years following human TBI [2,5,6,7,8,9,10,11]. Several pharmacological compounds such as antibodies targeting Nogo-A and/or its receptors have shown promising preclinical efficacy in axonal injury models, there are currently no treatment options with proven clinical efficacy available for DAI patients [13,14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
