Major organ-based in vitro diagnostic (IVD) tests like ALT/AST for the liver and cardiac troponins for the heart are established, but a regulatory-approved IVD blood test for the brain has been missing, highlighting a significant gap in medical diagnostics. In response to this need, Abbott Diagnostics secured FDA clearance in 2021 for the i-STAT Alinity™, a point-of-care plasma blood test for mild traumatic brain injury (TBI). i-STAT Alinity™ as well as the bioMerieux VIAD, also approved in Europe, utilizes two brain-derived protein biomarkers: neuronal ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP). These biomarkers, which are typically present in minimal amounts in healthy individuals, are instrumental in diagnosing mild TBI with potential brain lesions. The study explores how UCH-L1 and GFAP levels increase significantly in the bloodstream following traumatic brain injury, aiding in early and accurate diagnosis. The introduction of the i-STAT Alinity™ and the Biomerieux Vidas TBI blood tests mark a groundbreaking development in the field of TBI diagnosis. It paves the way for the integration of TBI biomarker tools into clinical practice and therapeutic trials, enhancing the precision medicine approach by generating valuable data. This advancement is a critical step in addressing the long-standing gap in brain-related diagnostics and promises to revolutionize the management and treatment of mild TBI.

Penetrating cortical impact injuries alter neuronal communication beyond the injury epicentre, across regions involved in affective, sensorimotor and cognitive processing. Understanding how traumatic brain injury reorganizes local and brain wide nodal interactions may provide valuable quantitative parameters for monitoring pathological progression and recovery. To this end, we investigated spontaneous fluctuations in the functional MRI signal obtained at 11.1 T in rats sustaining controlled cortical impact and imaged at 2- and 30-days post-injury. Graph theory-based calculations were applied to weighted undirected matrices constructed from 12 879 pairwise correlations between functional MRI signals from 162 regions. Our data indicate that on Days 2 and 30 post-controlled cortical impact there is a significant increase in connectivity strength in nodes located in contralesional cortical, thalamic and basal forebrain areas. Rats imaged on Day 2 post-injury had significantly greater network modularity than controls, with influential nodes (with high eigenvector centrality) contained within the contralesional module and participating less in cross-modular interactions. By Day 30, modularity and cross-modular interactions recover, although a cluster of nodes with low strength and low eigenvector centrality remain in the ipsilateral cortex. Our results suggest that changes in node strength, modularity, eigenvector centrality and participation coefficient track early and late traumatic brain injury effects on brain functional connectivity. We propose that the observed compensatory functional connectivity reorganization in response to controlled cortical impact may be unfavourable to brain wide communication in the early post-injury period.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites at A-56*A-61 and (ii) major C-terminal cleavage sites at T-383*Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78/R-79 and D-225/A-226, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.

Pristane causes chronic peritoneal inflammation resulting in lupus, which in C57BL/6 mice is complicated by lung microvascular injury and diffuse alveolar hemorrhage (DAH). Mineral oil (MO) also causes inflammation, but not lupus or DAH. Since monocyte depletion prevents DAH, we examined the role of monocytes in the disease. Impaired bone marrow (BM) monocyte egress in Ccr2−/− mice abolished DAH, confirming the importance of monocyte recruitment to the lung. Circulating Ly6C^hi monocytes from pristane-treated mice exhibited increased annexin-V staining in comparison with MO-treated controls without evidence of apoptosis, suggesting that pristane alters the distribution of phosphatidylserine in the plasma membrane before or shortly after monocyte egress from the BM. Plasma membrane asymmetry also was impaired in Nr4a1-regulated Ly6C^lo/− ‘patrolling’ monocytes, which are derived from Ly6C^hi precursors. Patrolling Ly6C^lo/− monocytes normally promote endothelial repair, but their phenotype was altered in pristane-treated mice. In contrast to MO-treated controls, Nr4a1-regulated Ly6C^lo/− monocytes from pristane-treated mice were CD138⁺, expressed more TremL4, a protein that amplifies TLR7 signaling, and exuberantly produced TNFα in response to TLR7 stimulation. TremL4 expression on these novel CD138⁺ monocytes was regulated by Nr4a1. Thus, monocyte CD138, high TremL4 expression, and annexin-V staining may define an activated/inflammatory subtype of patrolling monocytes associated with DAH susceptibility. By altering monocyte development, pristane exposure may generate activated Ly6C^hi and Ly6C^lo/− monocytes, contributing to lung microvascular endothelial injury and DAH susceptibility.

Cardiac tamponade typically results from fluid or gas collection in the pericardial space leading to impairment in the cardiac function. A 34 years old male patient presented to the ER after a fall from height. X-rays were done which showed no hemothorax or pneumothorax and multiple stable pelvic fractures. Computed tomography (CT) scan for trauma was done after stabilizing the patient and showed sternal fracture with a huge retrosternal hematoma. The patient was intubated immediately, and an Echocardiogram was ordered along with preparation to go to the operation room urgently due to high suspicion of a rare case of cardiac tamponade. but the patient had cardiac arrest and couldn't be revived despite the CPR effort. This is a very unusual presentation of cardiac tamponade, mediastinal hematoma leading to extra pericardial tamponade. CT scan is an effective method to diagnose extra pericardial tamponade. In addition, to the high clinical suspicion is required. The sole treatment of mediastinal hematoma is an urgent evacuation. A careful assessment with high clinical suspicion along with CT Scan is the best way to diagnose extra pericardial tamponade cause by sternal fracture.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites between A-56 and A-75, and (ii) major C-terminal cleavage sites between T-383 and Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78, R-79, D-266 and A-267, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.