Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to "composite" blast.
Bottom Line: 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.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.
Affiliation: Banyan Laboratories, Inc Alachua, FL, USA.
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.
No MeSH data available.
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Mentions: Our shock tube was designed and built to model a freely expanding blast wave as generated by a typical explosion. Both static and dynamic (total) pressures were measured as functions of angle and radial distance from shock tube exit using piezoelectric blast pressure transducers positioned at the target (Figure 1C). The pressure transducers registered three distinct events: (i) peak OP, (ii) gas venting jet-on-axis only, and (iii) negative pressure phase-off-axis only (Figures 1A,B). The exhaust of venting gas apparently distorted propagation of the blast wave and no negative phase was registered when dynamic pressure was measured on-axis of shock tube (Figure 1A), while a distinct and substantial negative phase (15–20 kPa) was detected off-axis (Figure 1B). Peak OP, positive phase duration, and impulse appear to be the key parameters that correlate to injury and likelihood of fatality in animals and humans, for various orientations of the specimen relative to the blast wave. A schematic of a shock tube nozzle and the alternative rat locations relative to the shock tube axis, blast OP wave, and gas venting cone is shown in Figure 1D. Shock tubes produce a “venting gas jet” immediately after the blast wave forms, substantially contaminating the blast wave in the direction of the shock tube axis (Figure 1D). In a composite blast setup, venting gas jet lasts the longest (up to ∼3–5 ms), albeit lower in magnitude than peak overpressure, represents the bulk of blast impulse, and possibly produces the most devastating impact. Schlieren optics (Figure 2A) demonstrated a strong downward head acceleration following the passage of peak overpressure which lasts 50–100 μs. However, cranial deformation was more severe during the gas venting phase, lasting up to 5 ms. This effect was eliminated by placing rats off-axis from the venting jet in a way that the main effect acting on the specimen is the peak overpressure event. The high speed recording coupled with Schlieren optical system visualized interaction of the blast wave with the animal head/body and revealed a negligible degree of acceleration at rat positioning “off-axis” toward shock tube (primary blast; Figure 2B). The pressure on the surface of rats was calibrated depending on the distance and angle from the nozzle of shock tube (Figure 1C).
No MeSH data available.