Cerebrospinal Fluid Biomarkers Are Associated With Glial Fibrillary Acidic Protein and αII-spectrin Breakdown Products in Brain Tissues Following Penetrating Ballistic-Like Brain Injury in Rats

Abstract

Treatments to improve outcomes following severe traumatic brain injury (TBI) are limited but may benefit from understanding subacute-chronic brain protein profiles and identifying biomarkers suitable for use in this time. Acute alterations in the well-known TBI biomarkers glial fibrillary acidic protein (GFAP), αII-spectrin, and their breakdown products (BDPs) have been well established, but little is known about the subacute-chronic post-injury profiles of these biomarkers. Thus, the current study was designed to determine the extended profile of these TBI-specific biomarkers both in brain tissue and cerebral spinal fluid (CSF). Protein abundance was evaluated in brain tissue samples taken from regions of interest and in CSF at 24 h, 3 days, 7 days, 1 month, and 3 months following severe TBI in rats. Results showed increased full length GFAP (GFAP-FL) and GFAP-BDPs starting at 24 h that remained significantly elevated in most brain regions out to 3 months post-injury. However, in CSF, neither GFAP-FL nor GFAP-BDPs were elevated as a consequence of injury. Regional-specific reduction in αII-spectrin was evident in brain tissue samples from 24 h through 3 months. In contrast, SBDP-145/150 was robustly elevated in most brain regions and in CSF from 24 h through 7 days. Correlation analyses revealed numerous significant relationships between proteins in CSF and brain tissue or neurological deficits. This work indicates that TBI results in chronic changes in brain protein levels of well-known TBI biomarkers GFAP, αII-spectrin, and their BDPs and that SBDP-145/150 may have utility as an acute-chronic biomarker.

Penetrating Ballistic-Like Brain Injury Leads to MicroRNA Dysregulation, BACE1 Upregulation, and Amyloid Precursor Protein Loss in Lesioned Rat Brain Tissues

“…Thus, APP positive cells likely contain a mixture of intact as well as cleaved peptides ( Burton et al, 2008 ; Wahrle et al, 2008 ; Muresan et al, 2009 ). The PBBI model does not replicate amyloidosis (plaques) per se , but it does lead to drastic fragmentation of many neuronal proteins ( DeDominicis et al, 2018 ), inclusive of APP as previously mentioned, in addition to tissue loss in a manner that is much more drastic than CCI or FPI ( Mountney et al, 2016 ).…”

“…This model has been extensively characterized; several studies have found that key features are generally highest at 1, 3, or 7 days post-injury. For instance, blood brain barrier disruption is greatest within 1 day ( Cunningham et al, 2014 ), while indices of inflammation, cell loss, and protein fragmentation are prominent at 3–7 days post-injury ( Boutte et al, 2016 , 2020 ; Cartagena et al, 2016 ; DeDominicis et al, 2018 ). Collectively, these features are involved in severe TBI progression for which miRNA may be involved.…”

Overpressure Exposure From .50-Caliber Rifle Training Is Associated With Increased Amyloid Beta Peptides in Serum

“…Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a deubiquitinating enzyme enriched in neuronal cell bodies (17). GFAP and UCH-L1 are the most widely used biomarkers for acute, moderate-to-severe TBI (18)(19)(20)(21). Tau, an important microtubule-associated structural element of the neuronal cytoskeleton (22).…”

Co-Expression Network Analysis of MicroRNAs and Proteins in Severe Traumatic Brain Injury: A Systematic Review

“…The same search filters were applied, leading to 295 results being excluded while a further 71 duplicates were removed using EndNote 20 [ 30 ]. A total of 140 papers were manually excluded following assessment against the selection criteria, leaving a total of 24 papers eligible for inclusion in the review [ 36 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. Figure 2 provides an overview of the protein literature search and study selection process.…”