Abstract 111: Myeloid Specific Deletion of CD36 Increases Microglia-Like CD45 Low Subset and Exacerbates Stroke-Induced Brain Injury

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Keun Woo Park ◽  
Mustafa Balkaya ◽  
Jiwon Yang ◽  
Sunghee Cho
Keyword(s):  
Brain Injury ◽  
Immune Cells ◽  
Infarct Volume ◽  
Recovery Process ◽  
Stroke Recovery ◽  
Beneficial Effects ◽  
Transient Focal Ischemia ◽  
Inflammation Resolution

Objective: CD36 regulates biological and pathological processes including inflammation, resolution, phagocytosis, and angiogenesis. Highly expressed in monocytes/macrophages (MM), MM CD36 has been implicated in both detrimental and beneficial effects in acute stroke outcome and recovery. Using myeloid specific deficiency of CD36 (CD36KO MM ) mice, the present study addresses the role of MM CD36 on subset composition of MM in the acute and recovery phases of stroke. Methods: WT (CD36 fl/fl ) and CD36KO MM (M/F, 12w old) mice were subjected to transient focal ischemia. Brain immune cells were collected at 3d, 7d and 2m (n=8-12/timepoint). Infarct volume and hemispheric swelling were measured at 3d (n=13/genotype). In the isolated brain immune cells, CD11b+ cells were further distinguished by CD45 Hi and CD45 Low subsets. The extent of MM trafficking was determined by an intravenous infusion of control GFP+ splenocytes into the stroked WT and CD36KO MM mice 1d prior to sacrifice and MM subset analyses. Results: Compared to WT mice, CD36KO MM mice showed no difference in CD45 Low subset at 3d, 7d and 2m after stroke. However, CD36KO MM mice displayed a significant reduction of CD45 Hi subset, presumably infiltrating cells, at these time points (n=4-8 /group, P<0.01). Adoptive transfer of control GFP+ splenocytes to stroked CD36KO MM mice resulted in an increase of GFP+ cells in CD45 Low but a profound reduction in CD45 Hi subset. Despite the near absence of CD45 Hi and increased CD45 Low population in the post-ischemic brain, CD36KO MM mice displayed exacerbation of brain injury (15.1±13.7 vs 25.8±17.5 mm 3 , p<0.05) and brain swelling (12.1±10.3 vs 18.4±12.7 %, p=0.1). Conclusion: The observed reduction of CD45 Hi subset and exacerbation of brain injury in CD36KO MM mice suggests a beneficial role of infiltrated CD45 Hi MMs in limiting stroke injury. The sustained trafficking at 2m indicates potential involvement of MM CD36 in the recovery process. Further studies to assess long-term outcomes of CD36KO MM mice will provide critical insights on the role of macrophage CD36 in stroke recovery.

scholarly journals RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 70
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Martha Villagran ◽  
Robert Zdanowski ◽  
Jacek Z. Kubiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Circadian Rhythm ◽  
Immune Cells ◽  
Chronic Rejection ◽  
Cardiac Transplantation ◽  
Small Gtpase ◽  
Eukaryotic Cells ◽  
Transplantation Model

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.

Neuroprotective Role of Nutritional Supplementation in Athletes

2021 ◽  
Vol 14 ◽  
Author(s):  
Supriya Mishra ◽  
Vikram Jeet Singh ◽  
Pooja A Chawla ◽  
Viney Chawla
Keyword(s):  
Neurodegenerative Disorders ◽  
Brain Injuries ◽  
Recovery Process ◽  
Traumatic Brain Injuries ◽  
Omega 3 ◽  
Long Run ◽  
Pathological Mechanism ◽  
Injury Recovery

Background: Neurodegenerative disorders belong to different classes of progressive/chronic conditions that affect the peripheral/central nervous system. It has been shown through studies that athletes who play sports involving repeated head trauma and sub-concussive impacts are more likely to experience neurological impairments and neurodegenerative disorders in the long run. Aims: The aim of the current narrative review article is to provide a summary of various nutraceuticals that offer promise in the prevention or management of sports-related injuries, especially concussions and mild traumatic brain injuries. Methods: This article reviews the various potential nutraceutical agents and their possible mechanisms in providing a beneficial effect in the injury recovery process. A thorough survey of the literature was carried out in the relevant databases to identify studies published in recent years. In the present article, we have also highlighted the major neurological disorders along with the associated nutraceutical(s) therapy in the management of disorders. Results: The exact pathological mechanism behind neurodegenerative conditions is complex as well as idiopathic. However, mitochondrial dysfunction, oxidative stress as well as intracellular calcium overload are some common reasons responsible for the progression of these neurodegenerative disorders. Owing to the multifaceted effects of nutraceuticals (complementary medicine), these supplements have gained importance as neuroprotective. These diet-based approaches inhibit different pathways in a physiological manner without eliciting adverse effects. Food habits and lifestyle of an individual also affect neurodegeneration. Conclusion: Studies have shown nutraceuticals (such as resveratrol, omega-3-fatty acids) to be efficacious in terms of their neuroprotection against several neurodegenerative disorders and to be used as supplements in the management of traumatic brain injuries. Protection prior to injuries is needed since concussions or sub-concussive impacts may trigger several pathophysiological responses or cascades that can lead to long-term complications associated with CNS. Thus, the use of nutraceuticals as prophylactic treatment for neurological interventions has been proposed.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

First-stroke recovery process: The role of family social support

2000 ◽  
Vol 81 (7) ◽  
pp. 881-887 ◽  
Author(s):  
Evie Tsouna-Hadjis ◽  
Kostas N. Vemmos ◽  
Nikolaos Zakopoulos ◽  
Stamatis Stamatelopoulos
Keyword(s):  
Social Support ◽  
Recovery Process ◽  
Stroke Recovery ◽  
Family Social Support

scholarly journals Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia

2021 ◽  
Vol 22 (24) ◽  
pp. 13609
Author(s):  
Lucas Wauters ◽  
Raúl Y. Tito ◽  
Matthias Ceulemans ◽  
Maarten Lambaerts ◽  
Alison Accarie ◽  
...  
Keyword(s):  
Functional Dyspepsia ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Potential Role ◽  
Short Term ◽  
Beneficial Effects ◽  
Rrna Sequencing ◽  
Before And After

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.

scholarly journals Role of the Dopaminergic System in the Striatum and Its Association With Functional Recovery or Rehabilitation After Brain Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Antonio Verduzco-Mendoza ◽  
Paul Carrillo-Mora ◽  
Alberto Avila-Luna ◽  
Arturo Gálvez-Rosas ◽  
Adriana Olmos-Hernández ◽  
...  
Keyword(s):  
Brain Injury ◽  
Functional Recovery ◽  
Dopaminergic System ◽  
Brain Structures ◽  
Receptor Activation ◽  
Important Goal ◽  
Dopaminergic Drugs ◽  
Beneficial Effects ◽  
Severe Tbi

Disabilities are estimated to occur in approximately 2% of survivors of traumatic brain injury (TBI) worldwide, and disability may persist even decades after brain injury. Facilitation or modulation of functional recovery is an important goal of rehabilitation in all patients who survive severe TBI. However, this recovery tends to vary among patients because it is affected by the biological and physical characteristics of the patients; the types, doses, and application regimens of the drugs used; and clinical indications. In clinical practice, diverse dopaminergic drugs with various dosing and application procedures are used for TBI. Previous studies have shown that dopamine (DA) neurotransmission is disrupted following moderate to severe TBI and have reported beneficial effects of drugs that affect the dopaminergic system. However, the mechanisms of action of dopaminergic drugs have not been completely clarified, partly because dopaminergic receptor activation can lead to restoration of the pathway of the corticobasal ganglia after injury in brain structures with high densities of these receptors. This review aims to provide an overview of the functionality of the dopaminergic system in the striatum and its roles in functional recovery or rehabilitation after TBI.

Sa2015 Traumatic Brain Injury and Intestinal Dysfunction: Investigating a Putative Role of the Brain-Gut Axis in Long-Term Consequences of Injury

2015 ◽  
Vol 148 (4) ◽  
pp. S-384
Author(s):  
Elise L. Ma ◽  
Allen Smith ◽  
Neemesh Desai ◽  
Alan Faden ◽  
Terez Shea-Donohue
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Putative Role ◽  
Long Term Consequences ◽  
The Brain

Systemic lupus erythematosus—management

2013 ◽  
pp. 938-947
Author(s):  
Ida Dzifa Dey ◽  
David Isenberg
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Immunosuppressive Drugs ◽  
Systemic Lupus ◽  
General Management ◽  
Autoimmune Rheumatic Disease ◽  
The Future

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with varied presentation and a disease course characterized by remission and flares. Over the last 50 years the prognosis of SLE has improved considerably. The introductions of corticosteroids and later of cytotoxic drugs, dialysis, and renal transplantation were the major contributors to this improvement. Nevertheless, the treatment and general management of lupus continues to present a challenge. While lupus may, for some patients, represent a relatively mild set of problems, many others require large doses of immunosuppressive drugs, which carry long-term concerns about side effects. New immunotherapeutic drugs, with actions more closely targeted to the immune cells and molecules involved in the pathogenesis of SLE, are being introduced and the future looks promising. The role of early atherosclerosis and cardiovascular disease as a cause of death in patients with SLE is increasingly recognized and will present further challenges in the future.

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