Svetlov Stanislav I, Prima Victor, Glushakova Olena, Svetlov Artem, Kirk Daniel R, Gutierrez Hector, Serebruany Victor L, Curley Kenneth C, Wang Kevin K W, Hayes Ronald L
Banyan Laboratories, Inc Alachua, FL, USA.
Front Neurol. 2012 Feb 9;3:15. doi: 10.3389/fneur.2012.00015. eCollection 2012.
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.
已经在啮齿动物和大型动物中建立了多种爆炸脑损伤的实验模型。然而，爆炸源的多样性和爆炸波生物物理学的复杂性使得关于损伤机制和生物标志物的数据难以分析和比较。最近，我们展示了大鼠相对于外部冲击管产生的爆炸的位置的重要性。在本研究中，我们进一步对导致中度创伤性脑损伤的爆炸进行了特征描述，并定义了“复合”爆炸和原发性爆炸暴露设置。纹影光学技术可视化了头部与外部冲击管产生的冲击波之间的相互作用，发现在将大鼠与冲击管轴向对齐时（复合爆炸）头部有强烈加速，但在离轴峰值超压暴露时颅骨运动可忽略不计（原发性爆炸）。评估了原发性爆炸撞击额头时的脑损伤特征，并与复合爆炸产生的损伤进行了比较。通过银染色发现，与复合爆炸相比，原发性爆炸后神经退行性变水平较低或可忽略不计。然而，在原发性爆炸和复合爆炸后均检测到海马中持续的胶质细胞增生以及循环中GFAP/CNPase的积累。此外，血管/内皮炎症标志物整合素α/β、可溶性细胞间粘附分子-1和L-选择素以及神经营养因子神经生长因子-β在爆炸后6小时内血清中升高，并在随后的7天内持续存在。相比之下，全身性白细胞介素-1、白细胞介素-10、趋化因子、神经内分泌肽食欲素A和血管内皮生长因子受体神经纤毛蛋白-2（NRP-2）主要在原发性爆炸暴露后升高。总之，在所有爆炸设置下主要病理途径的生物标志物均升高。在复合爆炸后发现神经胶质标志物最显著且持续的变化，而原发性爆炸引发了显著的全身性细胞因子/趋化因子、食欲素A和神经纤毛蛋白-2释放，特别是当原发性爆炸撞击未受保护身体的大鼠时。
