Gediminas Čepinskas

Verified

Gediminas verified their affiliation via an institutional email.

Learn more

Verified

Gediminas verified their affiliation via an institutional email.

Learn more

• Director-Centre for Critical Illness Research, London Health Sciences Centre Research Institute
• Professor (Full) at London Health Sciences Centre

Recent studies suggest that exogenously administered CO is beneficial for the resolution of acute inflammation. In this study, we assessed the role of CO liberated from a systemically administered tricarbonyldichlororuthenium-(II)-dimer (CORM-2) on modulation of liver inflammation during sepsis. Polymicrobial sepsis in mice was induced by cecal lig...

One of the cardinal signs of acute inflammation is neutrophil (PMN) emigration across the endothelium and into the affected tissue. We have previously shown that human PMN migration across human umbilical vein endothelial cell (HUVEC) monolayers is dependent on PMN-derived elastase. However, whether migrating PMN release elastase into the extracell...

Polymorphonuclear leukocyte (PMN)-derived myeloperoxidase (MPO) contributes to the pathophysiology of numerous systemic inflammatory disorders through: 1) direct peroxidation of targets and 2) producing strong oxidizing compounds, e.g. hypohalous acids, particularly hypochlorous acid, which furthers oxidant damage and contributes to the propagation...

Huvec: PMN co-cultures were perfused for additional 15 minutes with PMN-free medium containing CORM-401/inactive CORM-401. The experiments were videorecorded (phase-contrast microscopy), and PMN adhesion/migration were assessed off-line. In parallel, CORM-401-dependent modulation of PMN chemotaxis, F-actin expression/distribution, and actin-regula...

Objectives: Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patie...

In vitro cell culture experiments play an important role in medical research. Various cellular mechanisms and signaling pathways have been identified with in vitro experimental techniques. Unfortunately, the clinical and translational impact of these studies is often limited due to their inability to closely resemble physiological or pathophysiolog...

Background: Sepsis remains a leading cause of mortality in critical care. Despite extensive preclinical research on sepsis pathophysiology, the development of effective novel therapies has been largely unsuccessful. Key obstacles include limited construct validity of animal models (e.g. standard therapies not incorporated in model), insufficient me...

Investigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly proportional to protein abundance, and mechanistic pathways are interconnected and under constant feedback regulatory control, fun...

Background In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case–control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to...

Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-c...

Background Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes (T1D), arising from relative insulin deficiency and leading to hyperglycemia, ketonemia, and metabolic acidosis. Early detection and treatment are essential to prevent severe outcomes. This pediatric case–control study utilized plasma metabolomics to explore metabol...

Background COVID-19 is a complex, multi-system disease with varying severity and symptoms. Identifying changes in critically ill COVID-19 patients’ proteomes enables a better understanding of markers associated with susceptibility, symptoms, and treatment. We performed plasma antibody microarray and machine learning analyses to identify novel prote...

Background The Multi-System Inflammatory Syndrome in Children (MIS-C) can develop several weeks after SARS-CoV-2 infection and requires a distinct treatment protocol. Distinguishing MIS-C from SARS-CoV-2 negative sepsis (SCNS) patients is important to quickly institute the correct therapies. We performed targeted proteomics and machine learning ana...

Background Sepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large n...

Background: COVID-19 is a complex, multi-system disease with varying severity and symptoms. Identifying changes in critically ill COVID-19 patients’ proteomes enables a better understanding of markers associated with susceptibility, symptoms, and treatment. We performed plasma antibody microarray and machine learning analyses to identify novel biom...

Abstract Background Preclinical sepsis models have been criticized for their inability to recapitulate human sepsis and suffer from methodological shortcomings that limit external validity and reproducibility. The National Preclinical Sepsis Platform (NPSP) is a consortium of basic science researchers, veterinarians, and stakeholders in Canada unde...

Aims Long-COVID occurs after SARS-CoV-2 infection and results in diverse, prolonged symptoms. The present study aimed to unveil potential mechanisms, and to inform prognosis and treatment. Methods Plasma proteome from Long-COVID outpatients was analyzed in comparison to matched acutely ill COVID-19 (mild and severe) inpatients and healthy control...

Background: Preclinical sepsis models have been criticized for their inability to recapitulate human sepsis and suffer from methodological shortcomings that limit external validity and reproducibility. The National Preclinical Sepsis Platform (NPSP) is a consortium of basic science researchers, veterinarians, and stakeholders in Canada undertaking...

Background: Survivors of acute COVID-19 often suffer prolonged, diffuse symptoms post-infection, referred to as "Long-COVID". A lack of Long-COVID biomarkers and pathophysiological mechanisms limits effective diagnosis, treatment and disease surveillance. We performed targeted proteomics and machine learning analyses to identify novel blood biomar...

Aims Long-COVID occurs after SARS-CoV-2 infection and results in diverse, prolonged symptoms. The present study aims to determine the underlying mechanisms, and to inform prognosis and treatment. Methods Plasma proteome from Long-COVID outpatients was analyzed in comparison to acutely ill COVID-19 (mild and severe) inpatients and healthy control s...

Sepsis‐elicited immunosuppression elevates the risk of secondary infections. We used a clinically relevant mouse model and serial peripheral blood samples from patients to assess the antimicrobial activities of mucosa‐associated invariant T (MAIT) cells in sepsis. Hepatic and splenic MAIT cells from B6‐MAITCAST mice displayed increased CD69 express...

Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-mat...

Background Despite the high morbidity and mortality associated with sepsis, the relationship between the plasma proteome and clinical outcome is poorly understood. In this study, we used targeted plasma proteomics to identify novel biomarkers of sepsis in critically ill patients. Methods Blood was obtained from 15 critically ill patients with susp...

Critically ill patients infected with SARS-CoV-2 display adaptive immunity, but it is unknown if they develop cross-reactivity to variants of concern (VOCs). We profiled cross-immunity against SARS-CoV-2 VOCs in naturally infected, non-vaccinated, critically ill COVID-19 patients. Wave-1 patients (wild-type infection) were similar in demographics t...

Background: Long-COVID is characterized by prolonged, diffuse symptoms months after acute COVID-19. Accurate diagnosis and targeted therapies for Long-COVID are lacking. We investigated vascular transformation biomarkers in Long-COVID patients. Methods: A case-control study utilizing Long-COVID patients, one to six months (median 98.5 days) post...

TO THE EDITOR, Systemic inflammation, particularly in its most severe forms such as sepsis, is characterized by an overwhelming activation and extravasation of circulating leukocytes, for example, polymorphonuclear leukocytes (PMNs), that if unchecked, contribute to propagating systemic inflammation-associated tissue/organ injury and dysfunction....

The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glyc...

Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations o...

In sepsis-induced inflammation, polymorphonuclear neutrophils (PMNs) contribute to vascular dysfunction. The serine proteases proteinase 3 (PR3) and human leukocyte elastase (HLE) are abundant in PMNs and are released upon degranulation. While HLE’s role in inflammation-induced endothelial dysfunction is well studied, PR3’s role is largely uninvest...

A full understanding of the molecular mechanisms implicated in the etiopathogenesis of juvenile idiopathic arthritis (JIA) is lacking. A critical role for leukocyte proteolytic activity (e.g., elastase and cathepsin G) has been proposed. While leukocyte elastase’s (HLE) role has been documented, the potential contribution of proteinase 3 (PR3), a s...

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health care emergency. Anti-SARS-CoV-2 serological profiling of critically ill COVID-19 patients was performed to determine their humoral response. Blood was collected from critically ill ICU patients, either COVID-19 positive (+) or COVID-19 negative (−), to measure anti-SARS-C...

Introduction: COVID-19 is associated with a novel multi-system inflammatory syndrome that shares some characteristics with Kawasaki's Disease. The syndrome manifestation is delayed relative to COVID-19 onset, with a spectrum of clinical severity. Clinical signs may include persistent fever, gastrointestinal symptoms, cardiac inflammation and/or sho...

Objectives:. Coronavirus disease 2019 continues to spread worldwide with high levels of morbidity and mortality. We performed anticoronavirus immunoglobulin G profiling of critically ill coronavirus disease 2019 patients to better define their underlying humoral response. Design:. Blood was collected at predetermined ICU days to measure immunoglobu...

Introduction: Preclinical sepsis research has been frequently criticized for shortfalls that limit translational impact. These can broadly be classified into problems with construct validity and preclinical methodology, whereby small animal models inadequately recapitulate the complex human condition of sepsis and experimental design contains numer...

Background COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. F...

Abstract Objectives: Coronavirus disease 2019 continues to spread rapidly with high mortality. We performed metabolomics profiling of critically ill coronavirus disease 2019 patients to understand better the underlying pathologic processes and pathways, and to identify potential diagnostic/prognostic biomarkers. Design: Blood was collected at pred...

Objectives: Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic...

Background: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19 associated host response....

Background: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19 associated host response....

Objectives: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease...

Background COVID-19 is associated with a novel multi-system inflammatory syndrome that shares some characteristics with Kawasaki’s Disease. The syndrome manifestation is delayed relative to COVID-19 onset, with a spectrum of clinical severity. Clinical signs may include persistent fever, gastrointestinal symptoms, cardiac inflammation and/or shock....

Objective: Limb compartment syndrome (CS), a complication of trauma, results in muscle necrosis and cell death; ischemia and inflammation contribute to microvascular dysfunction and parenchymal injury. Carbon monoxide releasing molecule-3 (CORM-3) has been shown to protect microvascular perfusion and reduce inflammation in animal models of CS. The...

Endothelial cell responses to mechanical forces such as shear stress and tensile stress have been a subject of intense investigations. However, there is a substantial lack of studies addressing the effects/mechanism of hydrostatic pressure on endothelial cell function. It is known that pathologies such as venous congestion, compartment syndrome etc...

Sepsis is a systemic inflammatory response to known or suspected infection, and associated with microvascular dysfunction and capillary leak. The cause of capillary leak may be due to substances released by activated polymorphonuclear neutrophils (PMNs) that adhere to microvascular endothelial cells. Following binding, PMN often degranulate releasi...

Alveolar macrophages are key contributors to both the promotion and resolution of inflammation in the lung and are categorized into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. The change in M1/M2 balance has been reported in various pulmonary diseases and is a target for therapeutic intervention. The aim of this study was to assess...

Background: Carbon monoxide (CO) inhalation protects organ by reducing inflammation and cell death during transplantation processes in animal model. However, using CO in clinical transplantation is difficult due to its delivery in a controlled manner. A manganese-containing CORM-401 has recently been synthesized which can efficiently deliver 3 mol...

Objectives: Acute limb compartment syndrome, a complication of musculoskeletal trauma, results in muscle necrosis and cell death. Carbon monoxide, liberated from the carbon monoxide-releasing molecule-3, has been shown protective in a rat model of compartment syndrome. The purpose of this study was to test the effect of carbon monoxide-releasing m...

The NLRP3 inflammasome is an intracellular multiple-protein complex that controls the maturation and release of interleukin (IL)-1β and IL-18. Endogenous carbon monoxide (CO) is anti-inflammatory. The aim of this study was to assess the effects/mechanisms of CO-releasing molecule-3 (CORM-3)-dependent modulation of the NLRP3 inflammasome in cardiac...

Objective: Ischemia-reperfusion (IR) is a limb- and life-threatening complication of acute limb ischemia and musculoskeletal trauma. Carbon monoxide-releasing molecules (CORMs) have recently been shown to protect microvascular perfusion and to reduce inflammation and injury in various ischemic animal models. The purpose of this study was to examin...

Aims: Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs. Methods: Using a rat model of compart...

Objective: Diabetic ketoacidosis in children is associated with vasogenic cerebral edema, possibly due to the release of destructive polymorphonuclear neutrophil azurophilic enzymes. Our objectives were to measure plasma azurophilic enzyme levels in children with diabetic ketoacidosis, to correlate plasma azurophilic enzyme levels with diabetic ke...

Background Our previous work suggested that a newly synthesized Mn ²⁺ ‐based water‐soluble carbon monoxide (CO)‐releasing molecules (CORM401) interfered with PMN recruitment by inhibiting transendothelial migration across the endothelium. In this study, we further investigated the effects of CORM401 on PMN chemotaxis by an F‐actin‐dependent mechani...

Sepsis is a systemic inflammatory response to known or suspected infection, and associated with microvascular dysfunction and capillary leak. The cause of capillary leak may be due to substances released by activated polymorphonuclear neutrophils (PMNs) that adhere to microvascular endothelial cells. Following binding, PMN often degranulate releasi...

Background: Diabetic Ketoacidosis (DKA) in children is associated with cerebrovascular-related complications. We recently reported that DKA facilitates leukocyte adherence to the brain microvascular endothelium. Adhered leukocytes can release enzymes that instigate vascular dysfunction. Our aims were to measure plasma levels of leukocyte-derived m...

Background The outcome of the severe systemic disorders (e.g. sepsis, acute lung injury) largely depends on the efficacy of resolution of inflammation. We have reported that water-soluble carbon monoxide releasing molecule-3 (CORM-3) suppresses inflammatory activation in neutrophils and vascular endothelial cells and offers protection against sepsi...

A common complication of type-1 diabetes mellitus is diabetic ketoacidosis (DKA), a state of severe insulin deficiency. A potential harmful consequence of DKA therapy in children is cerebral edema (DKA-CE); however, the mechanisms of therapy-induced DKA-CE are unknown. Our aims were to identify the DKA treatment factors and membrane mechanisms that...

Sepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood brain barrier dysfunction. Thus, our objectives were (1) to measure inflammatory analytes in p...

Compartment syndrome, a devastating consequence of limb trauma, is characterised by severe tissue injury and microvascular perfusion deficits. We hypothesised that leucopenia might provide significant protection against microvascular dysfunction and preserve tissue viability. Using our clinically relevant rat model of compartment syndrome, microvas...

Introduction Diabetic ketoacidosis (DKA) is associated with cerebrovascular complications in children such as vasogenic edema. Circulating matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and other proteases may contribute to loss of cerebrovascular endothelial cell junctional integrity. Our aim was to determine the effects of...

Myeloperoxidase (MPO) binds to vascular endothelial cells (EC) through a mechanism that, at least in part, involves interactions with glycosaminoglycans expressed on the endothelial surface. MPO that is closely associated with endothelial cells can directly damage them through its catalytic activity. Our previous work demonstrated that carbon monox...

Background We have demonstrated that carbon monoxide (CO)‐releasing molecules (CORMs) reduce septic inflammation by interfering with PMN recruitment to the inflamed organs. In this study, we assessed the effects/mechanisms of a newly synthesized Mn ²⁺ ‐based water‐soluble CORM (CORM401) on PMN adhesion(A)/transendothelial migration(TM) in an experi...

Brain injury causes dysfunction of the blood–brain barrier (BBB). The BBB is comprised of perivascular astrocytes whose end-feet ensheath brain microvascular endothelial cells. We investigated trauma-induced morphological changes of human astrocytes (HA) and human cerebral microvascular endothelial cells (hCMEC/D3) in vitro, including the potential...

Objective Exogenously administered carbon monoxide (CO) interferes with polymorphonuclear leukocyte (PMN) recruitment to the inflamed organs. The mechanisms of CO-dependent modulation of vascular pro-adhesive phenotype, a key step in PMN recruitment, are unclear.Methods We assessed the effects/mechanisms of CO liberated from a water-soluble CORM-3...

Trauma is a leading cause of pediatric morbidity and mortality. The primary aims of trauma resuscitation are to restore intravascular volume and to optimize both organ perfusion and tissue oxygen delivery. The most common organ system injured in pediatric trauma is the brain, suffering direct mechanical insult and indirect reperfusion insult from r...

Aims The present study was to investigate the role of calpain in reactive oxygen species (ROS) production in endothelial cells and endothelium-dependent vascular dysfunction under experimental conditions of diabetes. Methods and results Exposure to high glucose activated calpain, induced apoptosis and reduced nitric oxide (NO) production without c...

Previous work has demonstrated that carbon monoxide releasing molecules (CORMs) suppress inflammation, however, the mechanisms are not well understood. Neutrophil (PMN)‐derived myeloperoxidase (MPO) is known to play a significant role in the pathophysiology of numerous inflammatory disorders through: 1) direct peroxidation and 2) producing hypohalo...

Background: The pathology of traumatic brain injury (TBI) is poorly understood, but likely involves blood‐brain barrier (BBB) dysfunction. The BBB is lined with microvascular endothelial cells, ensheathed by astrocyte endfeet. We investigated human astrocytes and endothelial cell responses to concussive injury in vitro. Methods: Concussive injury i...

The study is to examine the role of CO derived from CORM‐3 on NLRP3 inflammasome activation in cardiac fibroblast (CF) and its effect on cardiomyocyte apoptosis and myocardial dysfunction in mice with sepsis. Methods: CFs were primed with LPS and followed by ATP treatment with or without CORM‐3. CF NLRP3 expression and NLRP3 inflammasome activation...

To examine the protective effects of carbon monoxide (CO), liberated from a novel CO releasing molecule (CORM-3), on the function of compartment syndrome (CS)-challenged muscle in a rodent model, thus providing for a potential development of a pharmacologic adjunctive treatment for compartment syndrome. Wistar rats were randomized into 4 groups: sh...

Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications, possibly due to leukocyte-endothelial interactions. Our aim was to determine if DKA-induced inflammation promoted leukocyte adhesion to activated human cerebrovascular endothelium. Plasma was obtained from children with type-1 diabetes, either in acute D...

Recent findings indicate that carbon monoxide (CO) in non-toxic doses exerts a beneficial anti-inflammatory action in various experimental models. However, the precise anti-inflammatory mechanism of CO in the intestine remains unclear. Here, we assessed the effects of a novel water-soluble CO-releasing molecule, CORM-3, on trinitrobenzene sulfonic...

CO liberated from a water‐soluble CO‐releasing molecule (CORM‐3) suppresses sepsis‐induced inflammation. However, the exact mechanisms are poorly understood. In this study we examined the mechanisms of CORM‐3‐dependent modulation of PMN adhesion in an in vitro model of endotoxemia employing human‐derived cerebrovascular endothelial cells, hCMEC/D3...

Previous work has demonstrated that CORM‐derived carbon monoxide (CO) supresses inflammation. However, the mechanisms are not well understood. Neutrophil (PMN)‐derived myeloperoxidase (MPO) is known to play a significant role in the pathophysiology of numerous inflammatory disorders through: 1) direct peroxidation and 2) producing hypohalous acids,...

The mechanisms of severe sepsis induced activation/dysfunction of the cerebrovascular endothelium are poorly understood. Our findings indicate that severe sepsis in humans results in up‐regulation of 8 (p<0.01; out of 41 measured) inflammation‐relevant analytes in the blood plasma. We employed Severe sepsis Cytomix (SS‐CM) consisting of 8 cytokines...

Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications. The mechanisms of DKA‐induced vascular dysfunction are unclear. We aimed to assess the effects/mechanisms of DKA plasma on activation of human cerebrovascular endothelial cells (hCMEC/D3; provided by Dr. P.O. Couraud, INSERM). Methods DKA‐blood plasma w...

Concussive brain injury may directly injure cerebrovascular endothelial cells (CVEC) of the blood‐brain barrier and/or CVEC may be altered by circulating trauma‐induced inflammatory mediators. Thus, we assessed for activation of CVEC by either a concussive injury or by application of plasma from trauma patients. Methods Plasma was obtained from pe...

Translational research often involves tissue sampling and analysis. Blood is by far the most common tissue collected. Due to the many difficulties encountered with blood procurement from children, it is imperative to maximize the quality and stability of the collected samples to optimize research results. Collected blood can remain whole or be frac...

Objective: To determine if the DKA-induced inflammation in juvenile mice provokes activation and dysfunction of CVECs. Methods: DKA in juvenile mice was induced with administration of STZ and ALX. Blood from DKA mice was assessed for cytokines and soluble cell adhesion proteins, and either DKA plasma or exogenous compounds were applied to immort...

In the setting of acute lung injury, levels of circulating inflammatory mediators have been correlated with adverse outcomes. Previous studies have demonstrated that injured, mechanically ventilated lungs represent the origin of the host inflammatory response; however, mechanisms which perpetuate systemic inflammation remain uncharacterized. We hyp...

Purpose: Organ cold storage and subsequent transplantation are associated with significant ischemia-reperfusion injury, leading to cell death, graft inflammation and decreased graft function. Materials and methods: CORM-3s reduce oxidative stress and prevent inflammation in kidneys stored at 4C and subsequently transplanted. Graft survival and f...

What's known on the subject? and What does the study add? Hydrogen sulphide (H2S) has recently been classified as a member of the gasotransmitter family. Its physiological and pathophysiological effects are rapidly expanding with numerous studies highlighting the protective effects of H2S on ischaemia-reperfusion injury (IRI) in various organ syste...

Traumatic spinal cord injury (SCI) triggers a systemic inflammatory response (SIR) that contributes to a high incidence of secondary organ complications, particularly after a cervical or high-level thoracic injury. Because liver plays a key role in initiating and propagating the SIR, the aim of this study was to assess the effects that SCI at diffe...

The brain of the infant and young child is a developing, dynamic, structure subject to functional remodelling under the influence of factors responsible for optimal neuronal development and synaptogenesis. It exhibits age dependent variation in metabolic rate, blood flow, and ability to tolerate oxidative stress. It is also characterized by an exub...