Papers by Stefania Mondello
Cells
The proteome represents all the proteins expressed by a genome, a cell, a tissue, or an organism ... more The proteome represents all the proteins expressed by a genome, a cell, a tissue, or an organism at any given time under defined physiological or pathological circumstances. Proteomic analysis has provided unparalleled opportunities for the discovery of expression patterns of proteins in a biological system, yielding precise and inclusive data about the system. Advances in the proteomics field opened the door to wider knowledge of the mechanisms underlying various post-translational modifications (PTMs) of proteins, including glycosylation. As of yet, the role of most of these PTMs remains unidentified. In this state-of-the-art review, we present a synopsis of glycosylation processes and the pathophysiological conditions that might ensue secondary to glycosylation shortcomings. The dynamics of protein glycosylation, a crucial mechanism that allows gene and pathway regulation, is described. We also explain how—at a biomolecular level—mutations in glycosylation-related genes may lead ...
Advances and Technical Standards in Neurosurgery, 2014
Neurological disorders constitute a major health and socioeconomic problem. They represent the se... more Neurological disorders constitute a major health and socioeconomic problem. They represent the second cause of death and the leading cause of disability throughout the world. Despite the implementation of strategies and intervention programs to reduce the burden, over the past 25 years, the incidence, prevalence, mortality, and disability rates of neurological disorders are rising globally, mainly due to population aging and growth (1). This has placed heavy pressure on health-care systems pointing out the urgent need to identify new strategies to improve patient outcomes and reduce health costs by enabling more effective drug development and establishing a more personalized medicine approach. Rapid scientific and technical advances have enabled reliable and affordable measurement of novel biomarkers—biological indicators that objectively measure and evaluate physiological or pathophysiological processes or pharmacological responses to a therapeutic intervention (2)—which have been ...
Human Brain Mapping, 2020
Traumatic brain injury (TBI) is a major cause of disability worldwide, but the heterogeneous natu... more Traumatic brain injury (TBI) is a major cause of disability worldwide, but the heterogeneous nature of TBI with respect to injury severity and health comorbidities make patient outcome difficult to predict. Injury severity accounts for only some of this variance, and a wide range of preinjury, injury-related, and postinjury factors may influence outcome, such as sex, socioeconomic status, injury mechanism, and social support. Neuroimaging research in this area has generally been limited by insufficient sample sizes. Additionally, development of reliable biomarkers of mild TBI or repeated subconcussive impacts has been slow, likely due, in part, to subtle effects of injury and the aforementioned variability. The ENIGMA Consortium has established a framework for global collaboration that has resulted in the largest-ever neuroimaging studies of multiple psychiatric and neurological disorders. Here we describe the organization, recent progress, and future goals of the Brain Injury working group.
The Lancet, 2021
Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortali... more Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (U5MR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71•2 deaths per 1000 livebirths (95% uncertainty interval [UI] 68•3-74•0) in 2000 to 37•1 (33•2-41•7) in 2019 while global NMR correspondingly declined more slowly from 28•0 deaths per 1000 live births (26•8-29•5) in 2000 to 17•9 (16•3-19•8) in 2019. In 2019, 136 (67%) of 204 countries had a U5MR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030, 154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9•65 million (95% UI 9•05-10•30) in 2000 and 5•05 million (4•27-6•02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3•76 million [95% UI 3•53-4•02]) in 2000 to 48% (2•42 million; 2•06-2•86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0•80 (95% UI 0•71-0•86) deaths per 1000 livebirths and U5MR to 1•44 (95% UI 1•27-1•58) deaths per 1000 livebirths, and in 2019, there were as many as 1•87 million (95% UI 1•35-2•58; 37% [95% UI 32-43]) of 5•05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve U5MR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Funding Bill & Melinda Gates Foundation.
Journal of Proteome Research, 2020
Restless legs syndrome (RLS), also known as Willis-Ekbom Disease, is a sleep and neurological sen... more Restless legs syndrome (RLS), also known as Willis-Ekbom Disease, is a sleep and neurological sensorimotor disorder. The prevalence of RLS is at ~ 5%-15% in the general population. RLS could severely impact the daytime work productivity and the life quality of patients. However, the current diagnostic methods fail to provide an accurate and timely diagnosis, and the pathophysiology of RLS is not fully understood. Glycomics can help to unravel the underlying biochemical mechanisms of RLS, to identify specific glycome changes, and to develop powerful biomarkers for early detection and guiding interventions. Herein, we undertook a shotgun glycomics approach to determine and characterize the potential glycan biomarker candidates in the blood serum of RLS patients. Glycan profiles and isomeric quantitations were assessed by LC-MS analysis and compared with healthy controls. 24 N-glycan biomarker candidates show substantial differences between RLS patients and controls after the Benjamini-Hochberg multiple testing correction. Among those structures, glycans with the composition of HexNAc6Hex8Fuc1NeuAc2, HexNAc6Hex6Fuc1NeuAc3, and HexNAc5Hex6Fuc1NeuAc2 show the most significant alteration in expression profile (p < 0.001). Furthermore, 23 isomeric structures in the RLS cohorts show significant differences after the Benjamini-Hochberg multiple testing correction. HexNAc4Hex5Fuc1NeuAc2 (4512-3) and HexNAc6Hex7NeuAc3 (6703-1) (p < 0.001) were down expressed in the RLS cohort. HexNAc6Hex7NeuAc3 (6703-2) and HexNAc5Hex6NeuAc3 (5603-5) (p < 0.001) were expressed higher in the RLS cases. These results demonstrate that it is possible to detect specific glycome traits in individuals with RLS. The discovery of the N-glycan expression alterations might be useful in understanding the molecular mechanism of RLS, developing more refined and objective diagnostic methods, and discovering novel targeted therapeutic interventions.
The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significan... more The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significant and the heterogeneity of TBI patients and the relatively small sample sizes of most current neuroimaging studies is a major challenge for scientific advances and clinical translation. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Adult moderate/severe TBI (AMS-TBI) working group aims to be a driving force for new discoveries in AMS-TBI by providing researchers world-wide with an effective framework and platform for large-scale cross-border collaboration and data sharing. Based on the principles of transparency, rigor, reproducibility and collaboration, we will facilitate the development and dissemination of multiscale and big data analysis pipelines for harmonized analyses in AMS-TBI using structural and functional neuroimaging in combination with nonimaging biomarkers, genetics, as well as clinical and behavioral measures. Ultimately, we will offer investigators a...
Methods in molecular biology (Clifton, N.J.), 2017
Traumatic brain injury (TBI) is an injury to the brain caused by an external mechanical force, af... more Traumatic brain injury (TBI) is an injury to the brain caused by an external mechanical force, affecting millions of people worldwide. The disease course and prognosis are often unpredictable, and it can be challenging to determine an early diagnosis in case of mild injury as well as to accurately phenotype the injury. There is currently no cure for TBI-drugs having failed repeatedly in clinical trials-but an intense effort has been put to identify effective neuroprotective treatment. The detection of novel biomarkers, to understand more of the disease mechanism, facilitates early diagnosis, predicts disease progression, and develops molecularly targeted therapies that would be of high clinical interest. Over the last decade, there has been an increasing effort and initiative toward finding TBI-specific biomarker candidates. One promising strategy has been to use state-of-the-art neuroproteomics approaches to assess clinical biofluids and compare the cerebrospinal fluid (CSF) and bl...
Journal of Neurotrauma, 2016
Levetiracetam (LEV) is an anti-epileptic targeting novel pathways. Coupled with a favorable safet... more Levetiracetam (LEV) is an anti-epileptic targeting novel pathways. Coupled with a favorable safety profile and increasing empiric clinical use, it was the fifth drug tested by Operation Brain Trauma Therapy (OBTT). We assessed the efficacy of a single 15 min post-injury IV dose (54 or 170 mg/kg) on behavioral, histopathological, and biomarker outcomes after parasagittal fluid percussion brain injury (FPI), controlled cortical impact (CCI), and penetrating ballistic like brain injury (PBBI) in rats. In FPI, there was no benefit on motor function but on Morris water maze (MWM) both doses improved latencies and path lengths vs vehicle (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). On probe trial, the vehicle group was impaired vs sham, but both LEV treated groups did not differ vs sham, and the 54mg/kg group was improved vs vehicle (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). No histological benefit was seen. In CCI, there was a benefit on beam balance at 170mg/kg (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 vs vehicle). On MWM the 54 mg/kg dose was improved and not different from sham. Probe trial did not differ between groups for either dose. There was a reduction in hemispheric tissue loss (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 vs vehicle) with 170mg/kg. In PBBI there was no motor, cognitive or histological benefit from either dose. Regarding biomarkers, in CCI, 24h GFAP blood levels were lower in the 170mg/kg group vs vehicle (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). In PBBI, GFAP blood levels were increased in vehicle and 170mg/kg groups vs sham (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) but not in the 54mg/kg group. No treatment effects were seen for UCH-L1 across models. Early single IV LEV produced multiple benefits in CCI and FPI and reduced GFAP levels in PBBI. LEV achieved 10 points at each dose, is the most promising drug tested thus far by OBTT, and the only drug to improve cognitive outcome in any model. LEV has been advanced to testing in the micropig model in OBTT.
Journal of Neurotrauma, 2016
Nicotinamide (Vitamin B3) was the first drug selected for cross-model testing by the Operation Br... more Nicotinamide (Vitamin B3) was the first drug selected for cross-model testing by the Operation Brain Trauma Therapy (OBTT) consortium based on a compelling record of positive results in preclinical models of traumatic brain injury (TBI). Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI) or penetrating ballistic-like brain injury (PBBI). Nicotinamide (50 or 500 mg/kg) was delivered intravenously (IV) at 15m and 24h after injury with subsequent behavioral, biomarker and histopathological outcome assessments. There was an intermediate effect on balance beam performance with the high (500 mg/kg) dose in the CCI model, but no significant therapeutic benefit was detected on any other motor task across the OBTT TBI models. There was an intermediate benefit on working memory with the high dose in the FPI model. However, a negative effect of the low (50 mg/kg) dose was observed on cognitive outcome in the CCI model and no cognitive improvement was observed in the PBBI model. Lesion volume analysis showed no treatment effects after either FPI or PBBI, but the high dose of nicotinamide resulted in significant tissue sparing in the CCI model. Biomarker assessments included measurements of GFAP and UCH-LI in blood at 4 or 24 h after injury. Negative effects (both doses) were detected on biomarker levels of GFAP following FPI and on biomarker levels of UCH-L1 following PBBI. However, the high dose of nicotinamide reduced GFAP levels following both PBBI and CCI. Overall, our results showed a surprising lack of benefit from the low dose nicotinamide. In contrast, and partly in keeping with the literature, some benefit was achieved with the high dose. However, the marginal benefits achieved with nicotinamide, which appeared sporadically across the TBI models, reduced enthusiasm for further investigation by the OBTT Consortium.
Frontiers in Neuroengineering Series, 2015
Technology in Cancer Research & Treatment, 2015
Background: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-B... more Background: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. Patients and Methods: Patients with LpC having prostate volume ≤90 cm3 were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. Results: From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patie...
Brachytherapy, 2014
Aim of this study was to evaluate dose distribution within organs at risk (OARs) and planning tar... more Aim of this study was to evaluate dose distribution within organs at risk (OARs) and planning target volume (PTV) based on three-dimensional treatment planning according to two different setup positions in endometrial carcinoma patients submitted to postoperative brachy-radiotherapy on vaginal vault. Patients with endometrial cancer necessitating of adjuvant brachytherapy on vaginal vault were enrolled. Pelvic computed tomography studies were prospectively obtained in two different setup positions: extend legs (A position) and gynecological (B position). Contoured OARs were bladder, rectum, and small bowel. The PTV was identified as applicator&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s surface with an isotropic 5-mm margin expansion. Radiation dose delivered in 1 cc (D1cc) and 2 cc (D2cc) of OAR were calculated. Coverage of PTV and values of D1cc and D2cc obtained for bladder and small bowel were similar in the two positions. For rectum, both D1cc and D2cc had statistically significant lower values in A with respect to B position. Both in A and B positions, radiation doses delivered do not exceed the dose constraints. However, A setup seems to significantly reduce doses to rectum while obtaining the same PTV coverage. The findings from our study provide evidence supporting the use of A position setup for delivering vaginal vault brachytherapy.
Annals of Emergency Medicine, 2011
Among subjects with normal vital signs in triage, 28 admitted subjects have a lower mean ETCO2 th... more Among subjects with normal vital signs in triage, 28 admitted subjects have a lower mean ETCO2 than 82 discharged subjects: 30.5 vs. 33.0, mean difference 2.5, 95% CI 0.2-4.8, pϭ0.03. 7) One in 6 subjects presenting with normal vital signs and normal ETCO2 are admitted, while 1 in 2 subjects with normal vital signs and abnormal ETCO2 are admitted. 8) Mean ETCO2 is statistically different from normal in every diagnostic category Conclusion: Comparison between health care-seeking subjects and controls indicate that abnormal ETCO2 may be a sensitive (yet nonspecific) indicator of illness or injury. In the patient population, abnormal ETCO2 is predictive of need for hospital admission. Specificity of ETCO2 screening is improved by extending the range of accepted normal. Using this extended range, 1 in 3 patients with abnormal ETCO2 are admitted. However, only about 1 in 10 patients will present with an ETCO2 outside this extended range. Routine measurement of ETCO2 may contribute predictive information about severity of disease process that may be missed by current standard vital signs. Further studies need to be performed to assess whether specific patient populations may benefit more from triage ETCO2 screening.
ELECTROPHORESIS, 2016
As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitan... more As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or
Antioxidants, Oct 1, 2020
Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on sever... more Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.
The Lancet. Neurology, Dec 6, 2017
A commitment of governmental and non-governmental funding bodies, as well as industrial partners,... more A commitment of governmental and non-governmental funding bodies, as well as industrial partners, is needed to facilitate global collaborations and legacy research. Section 9 injuries. This accumulating knowledge makes it clear that TBI is not a single event, but can be a chronic and often progressive disease with long-term consequences. Even after an ostensibly good recovery, patients might have to live with a continuing process of coping and adaptation (panel 1). Panel 1: Living with traumatic brain injury a patient testimony In 2011, James Piercy sustained a traumatic brain injury (TBI) in a car accident in the UK. Like many people with TBI, he lives with the long-term effects of brain injury. He is now an ambassador for the UK Acquired Brain Injury Forum. In the following patient testimony (abridged), Piercy describes the aftermath of his injury and highlights what can be achieved with high-quality management and support. However, for many patients with TBI, systems of care are still suboptimal, poor, or even absent in some regions. For the full testimony, see appendix. The injury Like many others, I acquired my TBI in a car accident. I was unconscious at the scene (Glasgow Coma Scale score of 3 to 5). By good fortune, I was attended very soon after the accident by a police officer with good first-aid training. He kept my airway open until a doctor and paramedic from the air ambulance could take over my care. I was sedated and intubated at the scene before transfer to the local trauma centre. A scan revealed a bleed in my frontal lobe and smaller haemorrhages through the brain. Prognostic indicators gave a poor chance of good outcome after 6 months, but I have done better than expected. Better prognostic models for individual patients and families would be very valuable. I was monitored closely, emerging from post-traumatic amnesia after 25 days and transferring to a hospital closer to home. I was discharged after 7 weeks and began slow rehabilitation. The aftermath After 5 years, I am doing well. I have made a very good recovery and am back to work part-time. I need to plan my time carefully and avoid stressful and unpredictable situations, which leave me very fatigued. This fatigue can be very debilitating, leaving me with speech problems and making decisionmaking and concentration very difficult. Learning to live with the chronic conditions which follow TBI remains a huge challenge for the individuals and the services which aim to support them. I consider myself very lucky to have done so well and put the recovery down to good, prompt intervention, strong support from family and friends, and my own determination to improve. Clinical progress has not kept pace with the rising global burden of TBI and recognition of the prolonged effects of injury. The most recent major breakthrough in clinical management was the introduction of computed tomography (CT) scanning into routine care now more than 40 years ago. Since then, there have been no major improvements in outcome after TBI in HICs with developed trauma systems. This lack of progress can be attributed to many factors, both in thepolicy and clinical domains. Public and political awareness of the magnitude of the problems caused by TBI including the clinical impact on patients, families, and society, and public health burden and costs to society Cost Initial costs of some instruments and stipulation of payment per use Copyright Copyright issues and related difficulties in reproducing materials Access Restriction of some assessments to particular professional groups Scoring Charges and restrictions imposed by proprietary scoring systems Limited availability of many instruments in languages other than English is a major barrier to their use in international settings. Additionally, ensuring cultural applicability of assessment methods is an important challenge when collecting and analysing data across countries. The CANTAB and the
Antioxidants
Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on sever... more Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE ...
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Papers by Stefania Mondello