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Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to "composite" blast.

Svetlov SI, Prima V, Glushakova O, Svetlov A, Kirk DR, Gutierrez H, Serebruany VL, Curley KC, Wang KK, Hayes RL - Front Neurol (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Banyan Laboratories, Inc Alachua, FL, USA.

ABSTRACT
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.


Related in: MedlinePlus

Silver Staining of coronal brain sections following primary or “composite” blast exposure. Corresponding tissue staining 7 days after “composite blast,” primary blast, and CCI is shown in (A–C) for cortex, and in (D–F) for hippocampus. Arrowheads indicate occasional silver accumulation in the cells of non-neuronal origin. Arrows indicate diffuse silver accumulation in neurons. Figure 3A inset: a very rare accumulation of silver in a cortical neuron. Please see Section “Materials and Methods” for details.
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Figure 3: Silver Staining of coronal brain sections following primary or “composite” blast exposure. Corresponding tissue staining 7 days after “composite blast,” primary blast, and CCI is shown in (A–C) for cortex, and in (D–F) for hippocampus. Arrowheads indicate occasional silver accumulation in the cells of non-neuronal origin. Arrows indicate diffuse silver accumulation in neurons. Figure 3A inset: a very rare accumulation of silver in a cortical neuron. Please see Section “Materials and Methods” for details.

Mentions: As can be seen in Figure 3, composite blast (on-axis) produces silver accumulation at the seventh day post-blast (Figures 3A,D), particularly in the hippocampus (indicated by arrows). CCI also results in positive staining in ipsilateral cortex and hippocampus (Figures 3C,F). In contrast, there was a rare occurrence of silver accumulation observed in the cortex or hippocampus after exposure to primary blast (Figures 3B,E; indicated by arrowheads).


Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to "composite" blast.

Svetlov SI, Prima V, Glushakova O, Svetlov A, Kirk DR, Gutierrez H, Serebruany VL, Curley KC, Wang KK, Hayes RL - Front Neurol (2012)

Silver Staining of coronal brain sections following primary or “composite” blast exposure. Corresponding tissue staining 7 days after “composite blast,” primary blast, and CCI is shown in (A–C) for cortex, and in (D–F) for hippocampus. Arrowheads indicate occasional silver accumulation in the cells of non-neuronal origin. Arrows indicate diffuse silver accumulation in neurons. Figure 3A inset: a very rare accumulation of silver in a cortical neuron. Please see Section “Materials and Methods” for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275793&req=5

Figure 3: Silver Staining of coronal brain sections following primary or “composite” blast exposure. Corresponding tissue staining 7 days after “composite blast,” primary blast, and CCI is shown in (A–C) for cortex, and in (D–F) for hippocampus. Arrowheads indicate occasional silver accumulation in the cells of non-neuronal origin. Arrows indicate diffuse silver accumulation in neurons. Figure 3A inset: a very rare accumulation of silver in a cortical neuron. Please see Section “Materials and Methods” for details.
Mentions: As can be seen in Figure 3, composite blast (on-axis) produces silver accumulation at the seventh day post-blast (Figures 3A,D), particularly in the hippocampus (indicated by arrows). CCI also results in positive staining in ipsilateral cortex and hippocampus (Figures 3C,F). In contrast, there was a rare occurrence of silver accumulation observed in the cortex or hippocampus after exposure to primary blast (Figures 3B,E; indicated by arrowheads).

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.

View Article: PubMed Central - PubMed

Affiliation: Banyan Laboratories, Inc Alachua, FL, USA.

ABSTRACT
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.


Related in: MedlinePlus