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1.
Obesity (Silver Spring) ; 30(5): 982-993, 2022 May.
Article in English | MEDLINE | ID: mdl-35470973

ABSTRACT

The metabolic syndrome comprises a family of clinical and laboratory findings, including insulin resistance, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hypertension, in addition to central obesity. The syndrome confers a high risk of cardiovascular mortality. Indeed, metabolic dysfunction has been shown to cause a direct insult to smooth muscle and endothelial components of the vasculature, which leads to vascular dysfunction and hyperreactivity. This, in turn, causes cerebral vasoconstriction and hypoperfusion, eventually contributing to cognitive deficits. Moreover, the metabolic syndrome disrupts key homeostatic processes in the brain, including apoptosis, autophagy, and neurogenesis. Impairment of such processes in the context of metabolic dysfunction has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer, Parkinson, and Huntington diseases. The aim of this review is to elucidate the role that the metabolic syndrome plays in the pathogenesis of the latter disorders, with a focus on the role of perivascular adipose inflammation in the peripheral-to-central transduction of the inflammatory insult. This review delineates common signaling pathways that contribute to these pathologies. Moreover, the role of therapeutic agents aimed at treating the metabolic syndrome, as well as their risk factors that interfere with the aforementioned pathways, are discussed as potential interventions for neurodegenerative diseases.


Subject(s)
Insulin Resistance , Metabolic Syndrome , Neurodegenerative Diseases , Adipose Tissue/metabolism , Humans , Neurodegenerative Diseases/drug therapy , Obesity/complications , Obesity/drug therapy , Obesity/metabolism
2.
Biomedicines ; 10(2)2022 Jan 24.
Article in English | MEDLINE | ID: mdl-35203460

ABSTRACT

Traumatic brain injury (TBI) is a heterogeneous disease in its origin, neuropathology, and prognosis, with no FDA-approved treatments. The pathology of TBI is complicated and not sufficiently understood, which is the reason why more than 30 clinical trials in the past three decades turned out unsuccessful in phase III. The multifaceted pathophysiology of TBI involves a cascade of metabolic and molecular events including inflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. In this study, an open head TBI mouse model, induced by controlled cortical impact (CCI), was used to investigate the chronic protective effects of mitoquinone (MitoQ) administration 30 days post-injury. Neurological functions were assessed with the Garcia neuroscore, pole climbing, grip strength, and adhesive removal tests, whereas cognitive and behavioral functions were assessed using the object recognition, Morris water maze, and forced swim tests. As for molecular effects, immunofluorescence staining was conducted to investigate microgliosis, astrocytosis, neuronal cell count, and axonal integrity. The results show that MitoQ enhanced neurological and cognitive functions 30 days post-injury. MitoQ also decreased the activation of astrocytes and microglia, which was accompanied by improved axonal integrity and neuronal cell count in the cortex. Therefore, we conclude that MitoQ has neuroprotective effects in a moderate open head CCI mouse model by decreasing oxidative stress, neuroinflammation, and axonal injury.

3.
Sleep Sci ; 14(3): 236-244, 2021.
Article in English | MEDLINE | ID: mdl-35186202

ABSTRACT

OBJECTIVE: To study the effects of different psychotropic drugs on sleep architecture and sleep-related disorders. MATERIAL AND METHODS: In this retrospective review of 405 consecutive de-identified diagnostic polysomnograms performed at a sleep laboratory from 2007 until 2011, we grouped 347 polysomnograms into five categories: controls, antidepressants (AD), antidepressants + anticonvulsants (ADAC), antidepressants + antipsychotics (ADAP), antidepressants + anticonvulsants + antipsychotics (ADACP). We conducted pairwise comparisons for demographic characteristics, medical history, specific psychotropic medication uses and sleep architecture variables, and adjusted for multiple testing. We used logistic regression to determine the odds ratio of having elevated apnea-hypopnea index (AHI) and periodic limb movement index (PLMI) within each group as compared to controls. RESULTS: Compared to controls, all groups had a significantly higher prevalence of benzodiazepines and trazodone use. AD and ADACP had significantly longer REM latency and lower REM percentage of total sleep time compared to controls. ADAP had a significantly lower AHI compared to controls, but that association was lost in the regression model. AD was associated with a higher PLMI compared to controls. CONCLUSION: Psychotropic polypharmacy does not seem to be associated with significantly deleterious effects on sleep architecture. Adjunct anticonvulsants or antipsychotics to antidepressants may protect against periodic limb movement disorder.

4.
Rev Neurosci ; 33(3): 327-345, 2022 Apr 26.
Article in English | MEDLINE | ID: mdl-35170265

ABSTRACT

Traumatic brain injury (TBI) is a major cause of mortality and morbidity, affecting 2 million people annually in the US alone, with direct and indirect costs of $76.3 billion per year. TBI is a progressive disease with no FDA-approved drug for treating patients. Early, accurate and rapid diagnosis can have significant implications for successful triaging and intervention. Unfortunately, current clinical tests for TBI rely on CT scans and MRIs, both of which are expensive, time-consuming, and not accessible to everyone. Recent evidence of biofluid-based biomarkers being released right after a TBI incident has ignited interest in developing point-of-care (POC) platforms for early and on-site TBI diagnosis. These efforts face many challenges to accurate, sensitive, and specific diagnosis and monitoring of TBI. This review includes a deep dive into the latest advances in chemical, mechanical, electrical, and optical sensing systems that hold promise for TBI-POC diagnostic testing platforms. It also focuses on the performance of these proposed biosensors compared to biofluid-based orthodox diagnostic techniques in terms of sensitivity, specificity, and limits of detection. Finally, it examines commercialized TBI-POCs present in the market, the challenges associated with them, and the future directions and prospects of these technologies and the field.


Subject(s)
Biosensing Techniques , Brain Injuries, Traumatic , Biomarkers , Biosensing Techniques/methods , Brain Injuries, Traumatic/diagnosis , Humans , Point-of-Care Systems
5.
Nutr Rev ; 2022 Feb 16.
Article in English | MEDLINE | ID: mdl-35172003

ABSTRACT

The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials.

6.
Cells ; 11(3)2022 02 08.
Article in English | MEDLINE | ID: mdl-35159390

ABSTRACT

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 to neuropsychiatric manifestations and neurodegenerative disorders. We then analyze the shortcomings of glycoproteomic studies, putting into perspective their downfalls and the different advanced enrichment techniques that emanated to overcome some of these challenges. Furthermore, we summarize studies tackling the association between glycosylation and neuropsychiatric disorders and explore glycoproteomic changes in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington disease, multiple sclerosis, and amyotrophic lateral sclerosis. We finally conclude with the role of glycomics in the area of traumatic brain injury (TBI) and provide perspectives on the clinical application of glycoproteomics as potential diagnostic tools and their application in personalized medicine.


Subject(s)
Glycomics , Neurodegenerative Diseases , Biomarkers/metabolism , Humans , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Proteome , Proteomics/methods
7.
Neurochem Int ; 154: 105301, 2022 03.
Article in English | MEDLINE | ID: mdl-35121011

ABSTRACT

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Aspirin (ASA) and clopidogrel (CLOP) are antiplatelet agents that inhibit platelet aggregation. They are implicated in worsening the intracerebral haemorrhage (ICH) risk post-TBI. However, antiplatelet drugs may also exert a neuroprotective effect post-injury. We determined the impact of ASA and CLOP treatment, alone or in combination, on ICH and brain damage in an experimental rat TBI model. We assessed changes in platelet aggregation and measured serum thromboxane by enzyme immune assay. We also explored a panel of brain damage and apoptosis biomarkers by immunoblotting. Rats were treated with ASA and/or CLOP for 48 h prior to TBI and sacrificed 48 h post-injury. In rats treated with antiplatelet agents prior to TBI, platelet aggregation was completely inhibited, and serum thromboxane was significantly decreased, compared to the TBI group without treatment. TBI increases UCHL-1 and GFAP, but decreases hexokinase expression compared to the non-injured controls. All groups treated with antiplatelet drugs prior to TBI had decreased UCH-L1 and GFAP serum levels compared to the TBI untreated group. Furthermore, the ASA and CLOP single treatments increased the hexokinase serum levels. We confirmed that αII-spectrin cleavage increased post-TBI, with the highest cleavage detected in CLOP-treated rats. Aspirin and/or CLOP treatment prior to TBI is a double-edged sword that exerts a dual effect post-injury. On one hand, ASA and CLOP single treatments increase the post-TBI ICH risk, with a further detrimental effect from the ASA + CLOP treatment. On the other hand, ASA and/or CLOP treatments are neuroprotective and result in a favourable profile of TBI injury markers. The ICH risk and the neuroprotection benefits from antiplatelet therapy should be weighed against each other to ameliorate the management of TBI patients.


Subject(s)
Brain Injuries, Traumatic , Brain Injuries , Animals , Aspirin/pharmacology , Aspirin/therapeutic use , Brain Injuries/drug therapy , Brain Injuries, Traumatic/drug therapy , Clopidogrel/pharmacology , Humans , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Rats
8.
Exp Neurol ; 351: 113987, 2022 05.
Article in English | MEDLINE | ID: mdl-35065054

ABSTRACT

Traumatic brain injury (TBI) is a major cause of disability and death. Mild TBI (mTBI) constitutes ~75% of all TBI cases. Repeated exposure to mTBI (rmTBI), leads to the exacerbation of the symptoms compared to single mTBI. To date, there is no FDA-approved drug for TBI or rmTBI. This research aims to investigate possible rmTBI neurotherapy by targeting TBI pathology-related mechanisms. Oxidative stress is partly responsible for TBI/rmTBI neuropathologic outcomes. Thus, targeting oxidative stress may ameliorate TBI/rmTBI consequences. In this study, we hypothesized that mitoquinone (MitoQ), a mitochondria-targeted antioxidant, would ameliorate TBI/rmTBI associated pathologic features by mitigating rmTBI-induced oxidative stress. To model rmTBI, C57BL/6 mice were subjected to three concussive head injuries. MitoQ (5 mg/kg) was administered intraperitoneally to rmTBI+MitoQ mice twice per week over one month. Behavioral and cognitive outcomes were assessed, 30 days following the first head injury, using a battery of behavioral tests. Immunofluorescence was used to assess neuroinflammation and neuronal integrity. Also, qRT-PCR was used to evaluate the expression levels of antioxidant enzymes. Our findings indicated that MitoQ alleviated fine motor function and learning impairments caused by rmTBI. Mechanistically, MitoQ reduced astrocytosis, microgliosis, dendritic and axonal shearing, and increased the expression of antioxidant enzymes. MitoQ administration following rmTBI may represent an efficient approach to ameliorate rmTBI neurological and cellular outcomes with no observable side effects.

9.
Biomed Pharmacother ; 146: 112442, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35062053

ABSTRACT

Cancer is a leading cause of morbidity and mortality around the globe. Reactive oxygen species (ROS) play contradicting roles in cancer incidence and progression. Antioxidants have attracted attention as emerging therapeutic agents. Among these are flavonoids, which are natural polyphenols with established anticancer and antioxidant capacities. Increasing evidence shows that flavonoids can inhibit carcinogenesis via suppressing ROS levels. Surprisingly, flavonoids can also trigger excessive oxidative stress, but this can also induce death of malignant cells. In this review, we explore the inherent characteristics that contribute to the antioxidant capacity of flavonoids, and we dissect the scenarios in which they play the contrasting role as pro-oxidants. Furthermore, we elaborate on the pathways that link flavonoid-mediated modulation of ROS to the prevention and treatment of cancer. Special attention is given to the ROS-mediated anticancer functions that (-)-epigallocatechin gallate (EGCG), hesperetin, naringenin, quercetin, luteolin, and apigenin evoke in various cancers. We also delve into the structure-function relations that make flavonoids potent antioxidants. This review provides a detailed perspective that can be utilized in future experiments or trials that aim at utilizing flavonoids or verifying their efficacy for developing new pharmacologic agents. We support the argument that flavonoids are attractive candidates for cancer therapy.


Subject(s)
Antioxidants/pharmacology , Flavonoids/pharmacology , Reactive Oxygen Species/pharmacology , Carcinogens/chemistry , Flavonoids/chemistry , Humans , Neoplasms/prevention & control , Signal Transduction
10.
Cells ; 11(1)2022 01 04.
Article in English | MEDLINE | ID: mdl-35011725

ABSTRACT

Alzheimer's disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls. The aim of the study was to identify in the late stage of AD, the key dysregulated pathways that may contribute to pathogenesis and then to evaluate whether any of these pathways could be detected in the early phase of AD, opening new opportunity for early treatment that could stop or delay the pathology. Six common pathways were found regulated by miRNAs and proteins in the late stage of AD, with one of them (Rap1 signalling) activated since the early phase. MiRNAs and proteins were also compared to explore an inverse trend of expression which could lead to the identification of new therapeutic targets. These results suggest that specific miRNA changes could represent molecular fingerprint of neurodegenerative processes and potential therapeutic targets for early intervention.


Subject(s)
Alzheimer Disease/genetics , Brain/pathology , Gene Expression Profiling/methods , MicroRNAs/genetics , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Female , Humans , Male
11.
J Appl Toxicol ; 2022 Jan 09.
Article in English | MEDLINE | ID: mdl-35001415

ABSTRACT

Gasoline exposure has been widely reported in the literature as being toxic to human health. However, the exact underlying molecular mechanisms triggered by its inhalation have not been thoroughly investigated. We herein present a model of sub-chronic, static gasoline vapor inhalation in adult female C57BL/6 mice. Animals were exposed daily to either gasoline vapors (0.86 g/animal/90 min) or ambient air for 5 days/week over 7 consecutive weeks. At the end of the study period, toxic and molecular mechanisms underlying the inflammatory, oxidative, and apoptotic effects triggered by gasoline vapors, were examined in the lungs and liver of gasoline-exposed (GE) mice. Static gasoline exposure induced a significant increase (+21%) in lungs/body weight (BW) ratio in GE versus control (CON) mice along with a pulmonary inflammation attested by histological staining. The latter was consistent with increases in the transcript levels of proinflammatory cytokines [Interleukins (ILs) 4 and 6], respectively by ~ 6- and 4-fold in the lungs of GE mice compared to CON. Interestingly, IL-10 expression was also increased by ~ 10-fold in the lungs of GE mice suggesting an attempt to counterbalance the established inflammation. Moreover, the pulmonary expression of IL-12 and TNF-α was downregulated by 2- and 4-fold, respectively, suggesting the skewing toward Th2 phenotype. Additionally, GE mice showed a significant upregulation in Bax/Bcl-2 ratio, caspases 3, 8, and 9 with no change in JNK expression in the lungs, suggesting the activation of both intrinsic and extrinsic apoptotic pathways. Static gasoline exposure over seven consecutive weeks had a minor hepatic portal inflammation attested by H&E staining along with an increase in the hepatic expression of the mitochondrial complexes in GE mice. Therefore, tissue damage biomarkers highlight the health risks associated with vapor exposure and may present potential therapeutic targets for recovery from gasoline intoxication.

12.
BMJ Open ; 11(12): e057985, 2021 12 22.
Article in English | MEDLINE | ID: mdl-34937727

ABSTRACT

INTRODUCTION: Owing to their inherent vulnerabilities, the burden of COVID-19 and particularly of its control measures on migrants has been magnified. A thorough assessment of the value of the interventions for COVID-19 tailored to migrants is essential for improving their health outcomes as well as promoting an effective control of the pandemic. In this study, based on evidence from primary biomedical research, we aimed to systematically identify health interventions for COVID-19 targeting migrants and to assess and compare their effectiveness. The review will be conducted within a programme aimed at defining and implementing interventions to control the COVID-19 pandemic in Italy, funded by the Italian Ministry of Health and conducted by a consortium of Italian regional health authorities. METHODS AND ANALYSES: Data sources will include the bibliographic databases MEDLINE, Embase, LOVE Platform COVID-19 Evidence, and Cochrane Central Register of Controlled Trials. Eligible studies must evaluate health interventions for COVID-19 in migrants. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria, extract data of retained articles and assess methodological quality by applying the Cochrane Risk of Bias tool. Disagreements will be resolved through consensus or arbitrated by a third reviewer if necessary. In synthesising the evidence, we will structure results by interventions, outcomes and quality. Where studies are sufficiently homogenous, trial data will be pooled and meta-analyses will be performed. Data will be reported according to methodological guidelines for systematic review provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. ETHICS AND DISSEMINATION: This is a review of existing literature, and ethics approval is not required. We will submit results for peer-review publication and present at relevant conferences. The review findings will be included in future efforts to develop evidence-informed recommendations, policies or programmatic actions at the national and regional levels and address future high-quality research in public health.


Subject(s)
COVID-19 , Transients and Migrants , Humans , Pandemics , Research Design , Review Literature as Topic , SARS-CoV-2
13.
Front Pharmacol ; 12: 743059, 2021.
Article in English | MEDLINE | ID: mdl-34867349

ABSTRACT

Microglia, the resident phagocytes of the central nervous system and one of the key modulators of the innate immune system, have been shown to play a major role in brain insults. Upon activation in response to neuroinflammation, microglia promote the release of inflammatory mediators as well as promote phagocytosis. Plasma prekallikrein (PKall) has been recently implicated as a mediator of neuroinflammation; nevertheless, its role in mediating microglial activation has not been investigated yet. In the current study, we evaluate the mechanisms through which PKall contributes to microglial activation and release of inflammatory cytokines assessing PKall-related receptors and their dynamics. Murine N9-microglial cells were exposed to PKall (2.5 ng/ml), lipopolysaccharide (100 ng/ml), bradykinin (BK, 0.1 µM), and neuronal cell debris (16.5 µg protein/ml). Gene expression of bradykinin 2 receptor (B2KR), protease-activated receptor 2 (PAR-2), along with cytokines and fibrotic mediators were studied. Bioinformatic analysis was conducted to correlate altered protein changes with microglial activation. To assess receptor dynamics, HOE-140 (1 µM) and GB-83 (2 µM) were used to antagonize the B2KR and PAR-2 receptors, respectively. Also, the role of autophagy in modulating microglial response was evaluated. Data from our work indicate that PKall, LPS, BK, and neuronal cell debris resulted in the activation of microglia and enhanced expression/secretion of inflammatory mediators. Elevated increase in inflammatory mediators was attenuated in the presence of HOE-140 and GB-83, implicating the engagement of these receptors in the activation process coupled with an increase in the expression of B2KR and PAR-2. Finally, the inhibition of autophagy significantly enhanced the release of the cytokine IL-6 which were validated via bioinformatics analysis demonstrating the role of PKall in systematic and brain inflammatory processes. Taken together, we demonstrated that PKall can modulate microglial activation via the engagement of PAR-2 and B2KR where PKall acts as a neuromodulator of inflammatory processes.

14.
Curr Neuropharmacol ; 2021 Dec 02.
Article in English | MEDLINE | ID: mdl-34856905

ABSTRACT

Microglia are the resident immune cells of the brain and play a crucial role in housekeeping and maintaining homeostasis of the brain microenvironment. Upon injury or disease, microglial cells become activated, at least partly, via signals initiated by injured neurons. Activated microglia, thereby, contribute to both neuroprotection and neuroinflammation. However, sustained microglial activation initiates a chronic neuroinflammatory response which can disturb neuronal health and disrupt communications between neurons and microglia. Thus, microglia-neuron crosstalk is critical in a healthy brain as well as during states of injury or disease. As most studies focus on how neurons and microglia act in isolation during neurotrauma, there is a need to understand the interplay between these cells in brain pathophysiology. This review highlights how neurons and microglia reciprocally communicate under physiological conditions and during brain injury and disease. Furthermore, the modes of microglia-neuron communication are exposed, focusing on cell-contact dependent signaling and communication by the secretion of soluble factors like cytokines and growth factors. In addition, how microglia-neuron interactions could exert either beneficial neurotrophic effects or pathologic proinflammatory responses are discussed. We further explore how aberrations in microglia-neuron crosstalk may be involved in central nervous system (CNS) anomalies, namely: traumatic brain injury (TBI), neurodegeneration, and ischemic stroke. A clear understanding of how the microglia-neuron crosstalk contributes to the pathogenesis of brain pathologies may offer novel therapeutic avenues of brain trauma treatment.

15.
Expert Rev Mol Diagn ; 21(12): 1303-1321, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34783274

ABSTRACT

INTRODUCTION: Traumatic brain injury (TBI) is a major global health issue, resulting in debilitating consequences to families, communities, and health-care systems. Prior research has found that biomarkers aid in the pathophysiological characterization and diagnosis of TBI. Significantly, the FDA has recently cleared both a bench-top assay and a rapid point-of-care assays of tandem biomarker (UCH-L1/GFAP)-based blood test to aid in the diagnosis mTBI patients. With the global necessity of TBI biomarkers research, several major consortium multicenter observational studies with biosample collection and biomarker analysis have been created in the USA, Europe, and Canada. As each geographical region regulates its data and findings, the International Initiative for Traumatic Brain Injury Research (InTBIR) was formed to facilitate data integration and dissemination across these consortia. AREAS COVERED: This paper covers heavily investigated TBI biomarkers and emerging non-protein markers. Finally, we analyze the regulatory pathways for converting promising TBI biomarkers into approved in-vitro diagnostic tests in the United States, European Union, and Canada. EXPERT OPINION: TBI biomarker research has significantly advanced in the last decade. The recent approval of an iSTAT point of care test to detect mild TBI has paved the way for future biomarker clearance and appropriate clinical use across the globe.

16.
Neural Regen Res ; 17(6): 1228-1239, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34782556

ABSTRACT

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, it became evident that the SARS-CoV-2 virus infects multiple organs including the brain. Several clinical studies revealed that patients with COVID-19 infection experience an array of neurological signs ranging in severity from headaches to life-threatening strokes. Although the exact mechanism by which the SARS-CoV-2 virus directly impacts the brain is not fully understood, several theories have been suggested including direct and indirect pathways induced by the virus. One possible theory is the invasion of SARS-CoV-2 to the brain occurs either through the bloodstream or via the nerve endings which is considered to be the direct route. Such findings are based on studies reporting the presence of viral material in the cerebrospinal fluid and brain cells. Nevertheless, the indirect mechanisms, including blood-clotting abnormalities and prolonged activation of the immune system, can result in further tissue and organ damages seen during the course of the disease. This overview attempts to give a thorough insight into SARS-CoV-2 coronavirus neurological infection and highlights the possible mechanisms leading to the neurological manifestations observed in infected patients.

17.
Acute Med Surg ; 8(1): e696, 2021.
Article in English | MEDLINE | ID: mdl-34745637

ABSTRACT

Stroke is considered as the first cause of neurological dysfunction and second cause of death worldwide. Recombinant tissue plasminogen activator is the only chemical treatment for ischemic stroke approved by the US Food and Drug Administration. It was the only standard of care for a long time with a very narrow therapeutic window, which usually ranges from 3 to 4.5 h of stroke onset; until 2015, when multiple trials demonstrated the benefit of mechanical thrombectomy during the first 6 h. In addition, recent trials showed that mechanical thrombectomy can be beneficial up to 24 h if the patients meet certain criteria including the presence of magnetic resonance imaging/computed tomography perfusion mismatch, which allows better selectivity and higher recruitment of eligible stroke patients. However, magnetic resonance imaging/computed tomography perfusion is not available in all stroke centers. Hence, physicians need other easy and available diagnostic tools to select stroke patients eligible for mechanical thrombectomy. Moreover, stroke management is still challenging for physicians, particularly those dealing with patients with "wake-up" stroke. The resulting brain tissue damage of ischemic stroke and the subsequent pathological processes are mediated by multiple molecular pathways that are modulated by inflammatory markers and post-transcriptional activity. A considerable number of published works suggest the role of inflammatory and cardiac brain-derived biomarkers (serum matrix metalloproteinase, thioredoxin, neuronal and glial markers, and troponin proteins) as well as different biomarkers including the emerging roles of microRNAs. In this review, we assess the accumulating evidence regarding the current status of acute ischemic stroke diagnostic biomarkers that could guide physicians for better management of stroke patients. Our review could give an insight into the roles of the different emerging markers and microRNAs that can be of high diagnostic value in patients with stroke. In fact, the field of stroke research, similar to the field of traumatic brain injury, is in immense need for novel biomarkers that can stratify diagnosis, prognosis, and therapy.

19.
Front Immunol ; 12: 746168, 2021.
Article in English | MEDLINE | ID: mdl-34646273

ABSTRACT

Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults. The mortality rate is very high despite different treatments. New therapeutic targets are therefore highly needed. Cell-surface proteins represent attractive targets due to their accessibility, their involvement in essential signaling pathways, and their dysregulated expression in cancer. Moreover, they are potential targets for CAR-based immunotherapy or mRNA vaccine strategies. In this context, we investigated the GBM-associated surfaceome by comparing it to astrocytes cell line surfaceome to identify new specific targets for GBM. For this purpose, biotinylation of cell surface proteins has been carried out in GBM and astrocytes cell lines. Biotinylated proteins were purified on streptavidin beads and analyzed by shotgun proteomics. Cell surface proteins were identified with Cell Surface Proteins Atlas (CSPA) and Gene Ontology enrichment. Among all the surface proteins identified in the different cell lines we have confirmed the expression of 66 of these in patient's glioblastoma using spatial proteomic guided by MALDI-mass spectrometry. Moreover, 87 surface proteins overexpressed or exclusive in GBM cell lines have been identified. Among these, we found 11 specific potential targets for GBM including 5 mutated proteins such as RELL1, CYBA, EGFR, and MHC I proteins. Matching with drugs and clinical trials databases revealed that 7 proteins were druggable and under evaluation, 3 proteins have no known drug interaction yet and none of them are the mutated form of the identified proteins. Taken together, we discovered potential targets for immune therapy strategies in GBM.

20.
Mil Med ; 2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34632516

ABSTRACT

INTRODUCTION: Much of the research impacting diagnosis, outcome, and treatment of traumatic brain injuries (TBIs) has favored time of consciousness criteria indicative of hemispheric blast focus alone. However, recent animal-based research has widely expanded the diagnostic knowledge base and potential treatment options. METHODS: Recent animal-based research findings of foramen magnum and occipital crest-focused blast injuries in laboratory rats were reviewed and compared to the Part I human case report. RESULTS: Comparing the human case report (Part I) to that of animal research studies found very similar neuropathological outcomes, many deep and delayed, and supports why non-cerebral-focused TBIs have gone unrecognized. The overpressure wave is funneled through skull openings of the foramen magnum, with the possibility of a rebound secondary contrecoup injury impacting the orbits, oral-nasal cavity, and ears resulting in additional occult axonal and white matter injury. CONCLUSIONS: Research analysis prompted by a human case report (Part I) has helped identify mechanisms that assist in recognizing and defining non-cerebral hemispheric-focused TBI injuries. Position of the head in relationship to the blast wave, the setting in which the blast occurs, and close diagnostic follow-up are critical to the recognition, diagnosis, and treatment of injuries that have otherwise gone unrecognized and unstudied in humans since the Vietnam War.

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