Search

ObjectiveInconsistent evidence exists regarding the association between intraoperative hypothermia and incidence of surgical site infection (SSI). This study aimed to determine the association between intraoperative hypothermia and SSI.Materials and methodsA systematic review was conducted using Embase, PubMed, and Web of Science to identify observational studies evaluating the risk of SSI in patients with intraoperative hypothermia. The primary outcome measure was the diagnosis of SSI within 30 days of surgery. The pooled risk ratio was estimated using a fixed- or random-effect meta-analysis. Sensitivity analyses were performed to examine the impact of the structural design of preoperative warming on the pooled risk of SSI.ResultsFive studies representing 6,002 patients were included in the present meta-analysis. Intraoperative hypothermia was not associated with SSI risk in patients (HR = 1.22, 95% CI: 0.95–2.24, P = 0.119). The pooled hazard ratio showed that intraoperative hypothermia did not result in a higher risk of SSI.ConclusionsIntraoperative hypothermia was not associated with the risk of SSI. Further studies using objective exposure measurements are required to confirm these results.

Abstract Monocytes represent key cellular elements that contribute to the neurological sequela following brain injury. The current study reveals that trauma induces the augmented release of a transcriptionally distinct CD115+/Ly6Chi monocyte population into the circulation of mice pre-exposed to clodronate depletion conditions. This phenomenon correlates with tissue protection, blood–brain barrier stability, and cerebral blood flow improvement. Uniquely, this shifted the innate immune cell profile in the cortical milieu and reduced the expression of pro-inflammatory Il6, IL1r1, MCP-1, Cxcl1, and Ccl3 cytokines. Monocytes that emerged under these conditions displayed a morphological and gene profile consistent with a subset commonly seen during emergency monopoiesis. Single-cell RNA sequencing delineated distinct clusters of monocytes and revealed a key transcriptional signature of Ly6Chi monocytes enriched for Apoe and chitinase-like protein 3 (Chil3/Ym1), commonly expressed in pro-resolving immunoregulatory monocytes, as well as granule genes Elane, Prtn3, MPO, and Ctsg unique to neutrophil-like monocytes. The predominate shift in cell clusters included subsets with low expression of transcription factors involved in monocyte conversion, Pou2f2, Na4a1, and a robust enrichment of genes in the oxidative phosphorylation pathway which favors an anti-inflammatory phenotype. Transfer of this monocyte assemblage into brain-injured recipient mice demonstrated their direct role in neuroprotection. These findings reveal a multifaceted innate immune response to brain injury and suggest targeting surrogate monocyte subsets may foster tissue protection in the brain.

Abstract Background Efferocytosis is a process that removes apoptotic cells and cellular debris. Clearance of these cells alleviates neuroinflammation, prevents the release of inflammatory molecules, and promotes the production of anti-inflammatory cytokines to help maintain tissue homeostasis. The underlying mechanisms by which this occurs in the brain after injury remain ill-defined. Methods We used GFP bone marrow chimeric knockout (KO) mice to demonstrate that the axon guidance molecule EphA4 receptor tyrosine kinase is involved in suppressing MERTK in the brain to restrict efferocytosis of resident microglia and peripheral-derived monocyte/macrophages. Results Single-cell RNAseq identified MERTK expression, the primary receptor involved in efferocytosis, on monocytes, microglia, and a subset of astrocytes in the damaged cortex following brain injury. Loss of EphA4 on infiltrating GFP-expressing immune cells improved functional outcome concomitant with enhanced efferocytosis and overall protein expression of p-MERTK, p-ERK, and p-Stat6. The percentage of GFP+ monocyte/macrophages and resident microglia engulfing NeuN+ or TUNEL+ cells was significantly higher in KO chimeric mice. Importantly, mRNA expression of Mertk and its cognate ligand Gas6 was significantly elevated in these mice compared to the wild-type. Analysis of cell-specific expression showed that p-ERK and p-Stat6 co-localized with MERTK-expressing GFP + cells in the peri-lesional area of the cortex following brain injury. Using an in vitro efferocytosis assay, co-culturing pHrodo-labeled apoptotic Jurkat cells and bone marrow (BM)-derived macrophages, we demonstrate that efferocytosis efficiency and mRNA expression of Mertk and Gas6 was enhanced in the absence of EphA4. Selective inhibitors of ERK and Stat6 attenuated this effect, confirming that EphA4 suppresses monocyte/macrophage efferocytosis via inhibition of the ERK/Stat6 pathway. Conclusions Our findings implicate the ERK/Stat6/MERTK axis as a novel regulator of apoptotic debris clearance in brain injury that is restricted by peripheral myeloid-derived EphA4 to prevent the resolution of inflammation.

IntroductionThe panicle fertilization strategy for japonica and indica rice under wheat straw return (SR) has not been updated, especially on the elaboration of their impacts on spikelet differentiation and degeneration. This study aimed to verify the hypothesis that SR increases spikelet number by reducing spikelet degeneration and to explore the possibility of simplifying panicle fertilization.MethodsIn three consecutive years, four varieties of japonica and indica rice were field-grown in Yangzhou, Jiangsu Province, China. Six panicle fertilization rates and split treatments were applied to SR and no straw return (NR) conditions.ResultsThe results showed that SR promoted rice yield significantly by 3.77%, and the highest yields were obtained under the T2 (split panicle fertilization at the panicle initiation (PI) and spikelet primordium differentiation (SPD) stages) and T1 (panicle fertilization only at the PI stage) treatments, for indica and japonica rice, respectively. Correlation and path analysis revealed that the number of spikelets per panicle was the most attributable to yield variation. SR significantly increased the concentration of alkali hydrolyzable N in the soil 40 days after rice transplantation, significantly increased the nitrogen accumulation per stem (NA) during the SPD-pollen mother cell meiosis (PMC) stage, and increased the brassinosteroids level in the young panicles at the PMC stage. SR also reduced the degeneration rate of spikelets (DRS) and increased the number of surviving spikelets (NSS). The dry matter accumulation per stem was more important to increasing the NA in japonica rice at the PMC stage, whereas NA was more affected by the N content than the dry matter accumulation in indica rice. In japonica rice, panicle N application once only at the PI stage combined with the N released from SR was enough to improve the plant N content, reduce the DRS, and increase the NSS. For indica rice, split application of N panicle fertilization at both the PI and SPD stages was still necessary to achieve a maximum NSS.DiscussionIn conclusion, under wheat SR practice, panicle fertilization could be simplified to once in japonica rice with a significant yield increase, whereas equal splits might still be optimal for indica rice.

IntroductionPatients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency.MethodsThis cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing’s syndrome (BADx), 21 with Addison’s disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated.ResultsThe percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was upregulated in BADx and AD, but not in CAH patients (p < 0.0001). Although modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected.DiscussionIn patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment.

The widespread use of tetracycline (TC) poses potential hazards to ecosystems and human health. In this study, ZIF-67 was successfully synthesized using a room-temperature static synthesis method and applied to the efficient removal of TC from water. It was shown that the maximum adsorption of TC by ZIF-67 could reach 1583.128 mg·g−1 at pH = 5.0, an initial TC concentration of 450 mg·g−1, an adsorption time of 720 min, and a temperature of 308K.The pseudo-second-order kinetic model and Langmuir’s isothermal adsorption model could describe the adsorption process better, which proved that the adsorption of ZIF-67 on TC was mainly monolayer adsorption dominated by chemisorption. Mechanistic studies showed that the adsorption process of ZIF-67 on TC was mainly through electrostatic interactions, pore adsorption, π–π interactions, and framework coordination of ZIF-67 surface cations with TC.

We studied the effect of rockwool matrix on the conventional physical and chemical properties of soil and analyzed its toxicological effect on Eisenia fetida. The physical and chemical properties of rockwool were studied with characterization tests. By measuring earthworm enzymes and earthworm intestinal microorganisms, the effects of different rockwool particle sizes and additive amount on Eisenia fetida were analyzed. The results indicate that a low concentration of rockwool (Eisenia fetida, and played a positive role in improving the soil porosity. A high concentration of rockwool (>100 g/kg) reduced the exchangeable Ca and Mg content in the soil, and had a significant impact on the enzyme activity of Eisenia fetida. Mechanism studies have shown that high concentrations of rockwool (>200 g/kg) can have a significant impact on the nervous system of earthworm tissue. In addition, small particle size and low concentration of rockwool is conducive to the increase in intestinal microbial species of Eisenia fetida. This study clarifies the effects of emerging rockwool substrates on soil and soil organisms and provides theoretical support for the safe and reliable application of rockwool substrates in agricultural production.

Reasonable cropping systems and fertilizer management are vital for improving the quality of barren soil. The effectiveness of different crop rotation methods and fertilizers in soil improvement depends on various factors, including soil type, climate conditions, and crop type. In the present study, based on three rice-based cropping systems, the effects of organic fertilizers combined with slow-release fertilizers on rice yield and soil fertility in reclaimed soil were analyzed. The results showed that the rice grain yield was highest under the rice-fallow rotation system (RF) with the application of rapeseed meal fertilizer. Available nutrients such as AN, N_NH4+, TP, and AK showed a significant positive correlation with rice grain yield (p < 0.05). PCA and PERMANOVA analysis supported significant variation in CAZyme abundance among cropping systems (R2 = 0.60, p = 0.001) and significant differences between slow-release fertilizer treatments and organic fertilizer treatments (p < 0.05), but not among the three organic fertilizer treatments. Network analysis indicated positive stronger correlations among all functional enzymes in organic fertilizer treatments compared to chemical fertilizer treatments. RDA and correlation heat map results showed that C/N ratios and N_NH4+ were strongly related to CAZyme composition. PLS-PM analysis revealed that soil available nitrogen positively influenced several variables, while rice grain yield was negatively influenced by soil enzymes and TOC. These findings suggested that under appropriate cropping systems, partially substituting chemical fertilizers with organic fertilizers can effectively enhance the availability of nutrients in the soil, alter the activity of carbon-cycling microorganisms, and increase rice grain yield.

Circulating monocytes have emerged as key regulators of the neuroinflammatory milieu in a number of neuropathological disorders. Ephrin type A receptor 4 (Epha4) receptor tyrosine kinase, a prominent axon guidance molecule, has recently been implicated in the regulation of neuroinflammation. Using a mouse model of brain injury and a GFP BM chimeric approach, we found neuroprotection and a lack of significant motor deficits marked by reduced monocyte/macrophage cortical infiltration and an increased number of arginase-1+ cells in the absence of BM-derived Epha4. This was accompanied by a shift in monocyte gene profile from pro- to antiinflammatory that included increased Tek (Tie2 receptor) expression. Inhibition of Tie2 attenuated enhanced expression of M2-like genes in cultured Epha4-null monocytes/macrophages. In Epha4-BM–deficient mice, cortical-isolated GFP+ monocytes/macrophages displayed a phenotypic shift from a classical to an intermediate subtype, which displayed reduced Ly6chi concomitant with increased Ly6clo- and Tie2-expressing populations. Furthermore, clodronate liposome–mediated monocyte depletion mimicked these effects in WT mice but resulted in attenuation of phenotype in Epha4-BM–deficient mice. This demonstrates that monocyte polarization not overall recruitment dictates neural tissue damage. Thus, coordination of monocyte proinflammatory phenotypic state by Epha4 is a key regulatory step mediating brain injury.

Soil heavy metal pollution has become one of the major environmental issues of global concern and solving this problem is a major scientific and technological need for today’s socio-economic development. Environmentally friendly bioremediation methods are currently the most commonly used for soil heavy metal pollution remediation. Via controlled experiments, the removal characteristics of chromium from contaminated soil were studied using earthworms (Eisenia fetida and Pheretima guillelmi) and plants (ryegrass and maize) at different chromium concentrations (15 mg/kg and 50 mg/kg) in acidic and alkaline soils. The effects of chromium contamination on biomass, chromium bioaccumulation, and earthworm gut microbial communities were also analyzed. The results showed that E. fetida had a relatively stronger ability to remove chromium from acidic and alkaline soil than P. guillelmi, and ryegrass had a significantly better ability to remove chromium from acidic and alkaline soil than maize. The combined use of E. fetida and ryegrass showed the best effect of removing chromium from contaminated soils, wih the highest removal rate (63.23%) in acidic soil at low Cr concentrations. After soil ingestion by earthworms, the content of stable chromium (residual and oxidizable forms) in the soil decreased significantly, while the content of active chromium (acid-extractable and reducible forms) increased significantly, thus promoting the enrichment of chromium in plants. The diversity in gut bacterial communities in earthworms decreased significantly following the ingestion of chromium-polluted soil, and their composition differences were significantly correlated with soil acidity and alkalinity. Bacillales, Chryseobacterium, and Citrobacter may have strong abilities to resist chromium and enhance chromium activity in acidic and alkaline soils. There was also a significant correlation between changes in enzyme activity in earthworms and their gut bacterial communities. The bacterial communities, including Pseudomonas and Verminephrobacter, were closely related to the bioavailability of chromium in soil and the degree of chromium stress in earthworms. This study provides insights into the differences in bioremediation for chromium-contaminated soils with different properties and its biological responses.

Chemical fertilizers are commonly used to meet the nutritional demands of crops and boost their yields. However, their high costs and excessive application in soils increase the cost of production and have negative effects on the soil and environmental health. Vermicompost is an organic amendment that can potentially lessen the dependence on chemical fertilizers, with the additional advantages of sustainable nutrient supply to crops and maintaining soil health. To evaluate the potential of the two diverse vermicompost, the sole and combined applications of these vermicompost with reduced rates of chemical fertilizers were used for tomato cultivation in a field study. The results indicated that vermicompost produced from cattle manure combined with chemical fertilizers was more effective in improving tomato growth, physiology, yield, and nutritional attributes. Compared to the control treatment (NP applied), the combined application of vermicompost and chemical fertilizer significantly improved the root length (21.6%), plant height (167%), SPAD value (13.5%), chlorophyll ‘a’ (96%), chlorophyll ‘b’ (161%), relative water content (16%), membrane stability index (18%), carotenoid (87%), yield (82%), photosynthetic rate (148%), fruit diameter (83%), protein (89%), fat (27.5%), fiber (12%), vitamin C (52%), calcium (54%), magnesium (117%), phosphorus (38%) and potassium (128%). In addition, significant improvements in different soil physicochemical properties were also pragmatic. The results suggest that vermicompost application with reduced doses of chemical fertilizers can be used to improve crop yield and soil physico-chemical properties.

BackgroundInflammation is a significant contributor to neuronal death and dysfunction following traumatic brain injury (TBI). Recent evidence suggests that interferons may be a key regulator of this response. Our studies evaluated the role of the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) signaling pathway in a murine model of TBI.MethodsMale, 8-week old wildtype, STING knockout (−/−), cGAS−/−, and NLRX1−/− mice were subjected to controlled cortical impact (CCI) or sham injury. Histopathological evaluation of tissue damage was assessed using non-biased stereology, which was complemented by analysis at the mRNA and protein level using qPCR and western blot analysis, respectively.ResultsWe found that STING and Type I interferon-stimulated genes were upregulated after CCI injury in a bi-phasic manner and that loss of cGAS or STING conferred neuroprotection concomitant with a blunted inflammatory response at 24 h post-injury. cGAS−/− animals showed reduced motor deficits 4 days after injury (dpi), and amelioration of tissue damage was seen in both groups of mice up to 14 dpi. Given that cGAS requires a cytosolic damage- or pathogen-associated molecular pattern (DAMP/PAMP) to prompt downstream STING signaling, we further demonstrate that mitochondrial DNA is present in the cytosol after TBI as one possible trigger for this pathway. Recent reports suggest that the immune modulator NLR containing X1 (NLRX1) may sequester STING during viral infection. Our findings show that NLRX1 may be an additional regulator that functions upstream to regulate the cGAS-STING pathway in the brain.ConclusionsThese findings suggest that the canonical cGAS-STING-mediated Type I interferon signaling axis is a critical component of neural tissue damage following TBI and that mtDNA may be a possible trigger in this response.

Abnormalities in the prefrontal cortex (PFC), as well as the underlying white matter (WM) tracts, lie at the intersection of many neurodevelopmental disorders. The influence of microorganisms on brain development has recently been brought into the clinical and research spotlight as alterations in commensal microbiota are implicated in such disorders, including autism spectrum disorders, schizophrenia, depression, and anxiety via the gut-brain axis. In addition, gut dysbiosis is common in preterm birth patients who often display diffuse WM injury and delayed WM maturation in critical tracts including those within the PFC and corpus callosum. Microbial colonization of the gut aligns with ongoing postnatal processes of oligodendrogenesis and the peak of brain myelination in humans; however, the influence of microbiota on gyral WM development remains elusive. Here, we develop and validate a neonatal germ-free swine model to address these issues, as piglets share key similarities in WM volume, developmental trajectories, and distribution to humans. We find significant region-specific reductions, and sexually dimorphic trends, in WM volume, oligodendrogenesis, and mature oligodendrocyte numbers in germ-free piglets during a key postnatal epoch of myelination. Our findings indicate that microbiota plays a critical role in promoting WM development during early life when the brain is vulnerable to environmental insults that can result in an array of disabilities manifesting later in life.

Further promoting the application of lithium iron phosphate (LFP) requires both a high-rate performance and high volumetric energy density. Nanosizing and increased carbon content can improve rate performance but may decrease the volumetric energy density. Therefore, it is challenging to achieve both high volumetric energy density and excellent rate performance simultaneously for LFP. Here, we propose a heterogeneous spray-drying method to synthesize low-carbon-content hierarchical large microspheres filled with small microspheres composed of nanosized primary particles. The material was analyzed using X-ray diffraction, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, and in situ electrochemical impedance spectroscopy. The material exhibits a high tap density and excellent lithium-ion diffusion kinetics. Benefiting from the hierarchical large microsphere structure, the material maintains a capacity of 130.2 mA h g–1 at a rate of 10C and exhibits no capacity decay after 620 cycles at 1C. This study provides insights for the further promotion of LFP applications. [ABSTRACT FROM AUTHOR]

While originally identified as an antiviral pathway, recent work has implicated that cyclic GMP-AMP-synthase-Stimulator of Interferon Genes (cGAS-STING) signaling is playing a critical role in the neuroinflammatory response to traumatic brain injury (TBI). STING activation results in a robust inflammatory response characterized by the production of inflammatory cytokines called interferons, as well as hundreds of interferon stimulated genes (ISGs). Global knock-out (KO) mice inhibiting this pathway display neuroprotection with evidence that this pathway is active days after injury; yet, the early neuroinflammatory events stimulated by STING signaling remain understudied. Furthermore, the source of STING signaling during brain injury is unknown. Using a murine controlled cortical impact (CCI) model of TBI, we investigated the peripheral immune and microglial response to injury utilizing male chimeric and conditional STING KO animals, respectively. We demonstrate that peripheral and microglial STING signaling contribute to negative outcomes in cortical lesion volume, cell death, and functional outcomes postinjury. A reduction in overall peripheral immune cell and neutrophil infiltration at the injury site is STING dependent in these models at 24 h. Transcriptomic analysis at 2 h, when STING is active, reveals that microglia drive an early, distinct transcriptional program to elicit proinflammatory genes including interleukin 1-ß (IL-1ß), which is lost in conditional knock-out mice. The upregulation of alternative innate immune pathways also occurs after injury in these animals, which supports a complex relationship between brain-resident and peripheral immune cells to coordinate the proinflammatory response and immune cell influx to damaged tissue after injury. [ABSTRACT FROM AUTHOR]

Introduction: Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency. Methods: This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing’s syndrome (BADx), 21 with Addison’s disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated. Results: The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected. Discussion: In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment. [ABSTRACT FROM AUTHOR]

Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional EphA4f/f/Tie2-Cre and EphA4f/f/VE-Cadherin-CreERT2 knockout (KO) mice promotes blood–brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury. scRNAseq of capillary-derived KO ECs showed increased differential gene expression of BBB-related junctional and actin cytoskeletal regulators, namely, A-kinase anchor protein 12, Akap12, whose presence at Tie2 clustering domains is enhanced in KO microvessels. Transcript and protein analysis of CCI-injured whole cortical tissue or cortical-derived ECs suggests that EphA4 limits the expression of Cldn5, Akt, and Akap12 and promotes Ang2. Blocking Tie2 using sTie2-Fc attenuated protection and reversed Akap12 mRNA and protein levels cortical-derived ECs. Direct stimulation of Tie2 using Vasculotide, angiopoietin-1 memetic peptide, phenocopied the neuroprotection. Finally, we report a noteworthy rise in soluble Ang2 in the sera of individuals with acute TBI, highlighting its promising role as a vascular biomarker for early detection of BBB disruption. These findings describe a contribution of the axon guidance molecule, EphA4, in mediating TBI microvascular dysfunction through negative regulation of Tie2/Akap12 signaling. [ABSTRACT FROM AUTHOR]