Abstract
BackgroundSevere traumatic brain injury (TBI) has become a global health problem and causes a vast worldwide societal burden. However, distinct mechanisms between acute and subacute stages have not been systemically revealed. The present study aimed to identify differentially expressed proteins in severe TBI from the acute to subacute phase.MethodsSixty Sprague Dawley (SD) rats were randomly divided into sham surgery and model groups. The severe TBI models were induced by the controlled cortical impact (CCI) method. We evaluated the neurological deficits through the modified neurological severity score (NSS). Meanwhile, H&E staining and immunofluorescence were performed to assess the injured brain tissues. The protein expressions of the hippocampus on the wounded side of CCI groups and the same side of Sham groups were analyzed by the tandem mass tag-based (TMT) quantitative proteomics on the third and fourteenth days. Then, using the gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein–protein interaction (PPI), the shared and stage-specific differentially expressed proteins (DEPs) were screened, analyzed, and visualized. Eventually, target proteins were further verified by Western blotting (WB).ResultsIn the severe TBI, the neurological deficits always exist from the acute stage to the subacute stage, and brain parenchyma was dramatically impaired in either period. Of the significant DEPs identified, 312 were unique to the acute phase, 76 were specific to the subacute phase, and 63 were shared in both. Of the 375 DEPs between Sham-a and CCI-a, 240 and 135 proteins were up-regulated and down-regulated, respectively. Of 139 DEPs, 84 proteins were upregulated, and 55 were downregulated in the Sham-s and CCI-s. Bioinformatics analysis revealed that the differential pathophysiology across both stages. One of the most critical shared pathways is the complement and coagulation cascades. Notably, three pathways associated with gastric acid secretion, insulin secretion, and thyroid hormone synthesis were only enriched in the acute phase. Amyotrophic lateral sclerosis (ALS) was significantly enriched in the subacute stage. WB experiments confirmed the reliability of the TMT quantitative proteomics results.ConclusionOur findings highlight the same and different pathological processes in the acute and subacute phases of severe TBI at the proteomic level. The results of potential protein biomarkers might facilitate the design of novel strategies to treat TBI.
Highlights
Traumatic brain injury (TBI) is a significant cause of death and disability (Orešicet al., 2016)
To evaluate the neurological deficits of rats at the acute phase of severe TBI, modified neurological severity score (mNSS) was performed on the 3rd day
MNSS of the sham-operated group of subacute (Sham-s) group was considerably lower than that of Cortical Impact (CCI) (7.47 ± 2.264) on day 14 (p < 0.001) (Figure 2). These results indicated that the severe TBI models were established successfully
Summary
Traumatic brain injury (TBI) is a significant cause of death and disability (Orešicet al., 2016). The pathological mechanisms of TBI consist of primary injury and secondary injury (Maas et al, 2017). About 10% of TBI patients are considered severe, and the risk of secondary damage increases with severity (Ruet et al, 2021). Despite decades of effort to clarify the pathophysiology of TBI, the complex pathological mechanisms and biomarkers remain incompletely understood (Stocchetti and Maas, 2014; Irvine and Clark, 2018). Severe traumatic brain injury (TBI) has become a global health problem and causes a vast worldwide societal burden. The present study aimed to identify differentially expressed proteins in severe TBI from the acute to subacute phase
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
