Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts

Repeated blast-traumatic brain injury (blast-TBI) has
been hypothesized
to cause persistent and unusual neurological and psychiatric symptoms
in service members returning from war zones. Blast-wave primary effects
have been supposed to induce damage and molecular alterations in the
brain. However, the mechanisms through which the primary effect of
an explosive-driven blast wave generate brain lesions and induce
brain consequences are incompletely known. Prior findings from rat
brains exposed to two consecutive explosive-driven blasts showed molecular
changes (hyperphosphorylated-Tau, AQP4, S100β, PDGF, and DNA-polymerase-β)
that varied in magnitude and direction across different brain regions.
We aimed to compare, in an unbiased manner, the proteomic profile
in the hippocampus of double blast vs sham rats using mass spectrometry
(MS). Data showed differences in up- and down-regulation for protein
abundances in the hippocampus of double blast vs sham rats. Tandem
mass tag (TMT)-MS results showed 136 up-regulated and 94 down-regulated
proteins between the two groups (10.25345/C52B8VP0X). These TMT-MS findings revealed changes never described before
in blast studies, such as increases in MAGI3, a scaffolding protein
at cell–cell junctions, which were confirmed by Western blotting
analyses. Due to the absence of behavioral and obvious histopathological
changes as described in our previous publications, these proteomic
data further support the existence of an asymptomatic blast-induced
molecular altered status (ABIMAS) associated with specific protein
changes in the hippocampus of rats repeatedly expsosed to blast waves
generated by explosive-driven detonations.

重复性爆炸型颅脑创伤（blast-TBI）既往被学界提出假说，认为可导致从战区返国的军人出现持续性且非典型的神经与精神症状。既往研究认为，冲击波原发效应可造成脑部损伤与分子层面改变，但由爆炸驱动的冲击波原发效应如何引发脑部损伤并造成后续脑部病变的具体机制，目前仍未完全阐明。此前针对暴露于两次连续爆炸冲击波的大鼠脑部的研究显示，其脑部存在多种分子改变（磷酸化Tau蛋白、AQP4、S100β、PDGF以及DNA聚合酶-β），且这些改变的幅度与方向在不同脑区存在差异。本研究旨在通过无偏倚的方式，采用质谱（MS）技术对比两次爆炸暴露组与假手术组大鼠海马体的蛋白质组学特征。研究数据表明，两组大鼠海马体的蛋白丰度存在显著上调与下调差异。串联质谱标签（TMT）-质谱分析结果显示，两组间共有136个蛋白上调、94个蛋白下调（10.25345/C52B8VP0X）。本次串联质谱分析的结果揭示了此前爆炸创伤研究中从未被报道过的蛋白变化，例如细胞间连接脚手架蛋白MAGI3的表达上调，该结果已通过蛋白质免疫印迹（Western blotting）分析得到验证。由于本团队既往发表的研究中未观察到行为学与明显的组织病理学改变，本次蛋白质组学数据进一步支持了"无症状性爆炸诱导分子改变状态（ABIMAS）"的存在——该状态与反复暴露于爆炸冲击波的大鼠海马体中出现的特异性蛋白变化相关。