Temporal changes of neurobehavior in rats following varied blast magnitudes and screening of serum biomarkers in early stage of brain injury

Abstract

Blast neurotrauma has been linked to impairments in higher-order cognitive functions, including memory, attention, and mood. Current literature is limited to a single overpressure exposure or repeated exposures at the same level of overpressure. In this study, a rodent model of primary blast neurotrauma was employed to determine the pressure at which acute and chronic neurological alterations occurred. Three pressure magnitudes (low, moderate and high) were used to evaluate injury thresholds. A biology shock tube (BST) was used to simulate shock waves with overpressures of 60 kPa, 90 kPa and 120 kPa respectively. Neurological behavior of the rats was assessed by the Multi-Conditioning System (MCS) at 1 d, 7 d, 28 d and 90 d after shock wave exposure. Serum dopamine (DA), 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA) were measured at the same time points. The proteomic analysis was conducted to identify potentially vulnerable cellular and molecule targets of serum in the immediate post-exposure period. Results revealed that: (1) Anxiety-like behavior increased significantly at 1 d post-exposure in the medium and high overpressure (90 kPa, 120 kPa) groups, returned to baseline at 7 days, and anxiety-like behavior in the high overpressure groups re-emerged at 28 d and 90 d. (2) High overpressure (120 kPa) impaired learning and memory in the immediate post-exposure period. (3) The serum DA levels decreased significantly at 1 d post-exposure in the medium and high overpressure groups; The 5-HT levels decreased significantly at 1 d and 90 d in the high overpressure groups; The BDNF levels decreased significantly at 90 d in the high overpressure groups. (4) Proteomic analysis identified 38, 306, and 57 differentially expressed proteins in serum following low, medium and high overpressure exposures, respectively. Two co-expressed proteins were validated. Functional analysis revealed significant enrichment of 1121, 2096, and 1121 Gene Ontology (GO) items and 33, 47, and 26 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating extensive molecular responses to overpressure in the early phase. These findings suggest that exposure, even at moderate levels, can induce persistent neurobehavioral and molecular alterations, highlighting the need for further research into the long-term consequences of blast neurotrauma.