The proposed model of controlled nonpenetrating blast in rats demonstrates the critical pathologic and biochemical signatures of blast brain injury that may be triggered by cerebrovascular responses, including blood-brain barrier disruption, glia responses, and neuroglial alterations.

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.

The nature of warfare in the 21st century has led to a significant increase in primary blast or over-pressurization injuries to the whole body and head, which manifest as a complex of neuro-somatic damage, including traumatic brain injury (TBI). Identifying relevant pathogenic pathways in reproducible experimental models of primary blast wave exposure is therefore vital to the development of biomarkers for diagnostics of blast brain injury. Comparative analysis of mechanisms and putative biomarkers of blast brain injury is complicated by a deficiency of experimental studies. In this article, we present an overview of current TBI biomarkers, as well as outline experimental strategies to investigate molecular signatures of blast neurotrauma and to develop a pathway network map for novel biomarker discovery. These biomarkers will be effective for triaging and managing both combat and civilian casualities.

No abstract

No abstract

No abstract

No abstract

No abstract