Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts

Abstract

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.

Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics

“…Traumatic Brain Injury (TBI), a significant global health challenge, is a leading cause of death and disability worldwide, affecting an estimated 60 million individuals globally each year [ 1 ]. Despite extensive research spanning decades and numerous therapeutic strategies focusing on neuroprotection, neurovascular regeneration, and neuro-restoration, discovering a truly effective therapy for TBI remains a formidable challenge.…”

“…The hippocampus, a key area for memory, is notably impacted by TBI, particularly in maintaining synaptic plasticity and neurogenesis, often leading to impaired memory functions [ 6 , 7 ]. The impact on the hippocampus, its subregions, and connected neural pathways can selectively influence specific sensory-modalities, consequently affecting certain memory-related behaviors [ 1 ]. These behaviors and altered memory plasticity are commonly reported as future clinical manifestations following TBI, such as parkinsonism [ 8 , 9 ].…”

“…In addition, changes in expression levels of MAGI3 observed in hippocampal proteomics post TBI are linked to a wide series of molecular and biological system interactors. These changes may be related to short-term neuroplasticity phenomena or long-term neurodegenerative consequences such as parkinsonism [ 1 ]. As a site active in neurogenesis, immature new neurons in the hippocampal dentate gyrus (DG) subregion of mice have been shown to be vulnerable to injury, exhibiting significant degeneration as early as 2 days post-injury [ 11 ] and are likely to undergo apoptosis [ 12 ].…”