A number of experimental models of blast
brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and
biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position toward blast generated by an external
shock tube. In this study, we further characterized blast producing moderate
traumatic brain injury and defined "composite" blast and primary blast exposure set-ups. Schlieren optics visualized interaction between the head and a
shock wave generated by external
shock tube, revealing strong head acceleration upon positioning the rat on-axis with the
shock tube (composite blast), but negligible skull movement upon peak overpressure exposure off-axis (primary blast).
Brain injury signatures of a primary blast hitting the frontal head were assessed and compared to damage produced by composite blast. Low to negligible levels of neurodegeneration were found following primary blast compared to composite blast by
silver staining. However, persistent
gliosis in hippocampus and accumulation of GFAP/
CNPase in circulation was detected after both primary and composite blast. Also, markers of vascular/endothelial
inflammation integrin alpha/beta, soluble
intercellular adhesion molecule-1, and
L-selectin along with
neurotrophic factor nerve growth factor-beta were increased in serum within 6 h post-blasts and persisted for 7 days thereafter. In contrast, systemic
IL-1,
IL-10,
fractalkine, neuroendocrine
peptide Orexin A, and
VEGF receptor Neuropilin-2 (NRP-2) were raised predominantly after primary blast exposure. In conclusion,
biomarkers of major pathological pathways were elevated at all blast set-ups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic
cytokine/
chemokine,
Orexin A, and
Neuropilin-2 release, particularly when primary blast impacted rats with unprotected body.