Abstract W P98: Monocyte Chemotactic Protein-3 Elevated in Stoke and Aging

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Courtney A Townshend ◽  
Edward C Koellhoffer ◽  
Jeremy Grenier ◽  
Anjali Chauhan ◽  
Sharon DiMauro ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Tissue ◽  
Immune Cell ◽  
The Body ◽  
Cell Trafficking ◽  
Serum Samples ◽  
Post Stroke ◽  
Monocyte Chemotactic Protein ◽  
Aged Brain ◽  
Chemotactic Protein

Background: It is now recognized that stroke is a systemic stressor that triggers profound changes throughout the body, leading to alterations in the immune system and response. In the CNS, cell death from ischemic stroke activates glial cells, leading to trafficking of leukocytes into the brain and subsequent inflammation. Chemokines play an active role in modulating this recruitment process. Monocyte chemotactic protein-3 (MCP-3), also known as CCL7, is a chemokine that attracts a broad spectrum of immune cells. Although secreted at lower levels than the better-understood monocyte chemotactic protein-1, MCP-3 is released after injury and regulates migration of leukocytes, thus facilitating inflammation. As neuroinflammation is a well-documented complication after ischemic stroke, we hypothesized that MCP-3 levels would be elevated after stroke. In light of the fact that age is the principle risk factor for stroke, and that a chronic pro-inflammatory milieu is associated with aging, we also hypothesized that MCP-3 would increase with age. Methods: Young (10 weeks) and aged (18 months) male C57B16 mice were subjected to transient (60 minute) middle cerebral artery occlusion (MCAO) or a sham surgery. MCP-3 protein levels in brain tissue and serum samples from these stroked mice, as well as from cohorts of young and aged naïve mice, were analyzed with an ELISA. Results: The comparisons of naïve aged (n=4, mean=0.042±0.005 pg/μg) to naïve young (n=4, mean=0.017±0.009 pg/μg) mice showed a significant increase (p<.01) in MCP-3 in aged brain tissue. Additionally, when comparing aged MCAO to young MCAO (n=3, mean=0.01±0.007 pg/μg), MCP-3 was significantly elevated (p<.01) in the aged group. In comparing aged MCAO (n=6, mean=0.31±0.11 pg/ug ) to aged sham (n=6, mean=0.03±0.006 pg/μg), MCP-3 was significantly elevated (p<.05). No significant differences in MCP-3 levels in serum or between young stroke and young sham brain were seen. Conclusions: We demonstrated that levels of MCP-3 are increased post-stroke in aged mice, but not in young mice. Given what is known about the role of MCP-3 in immune cell trafficking, our data imply that MCP-3 plays a role in inflammation post-stroke, and that it also primes the aged brain for a greater inflammatory response post-stroke.

scholarly journals Place and Possibilities of the Robotic System Lokomat in the Rehabilitation of Patients After Ischemic Stroke

2019 ◽  
Vol 12 (1) ◽  
pp. 131-140
Author(s):  
Medvedev I. N.
Keyword(s):  
Ischemic Stroke ◽  
Robotic System ◽  
The Body ◽  
High Tech ◽  
Comprehensive Treatment ◽  
Common Disease ◽  
Main Task ◽  
Early Recovery ◽  
Modern Approach ◽  
Post Stroke

Ischemic stroke is still a very common disease with quite serious consequences. Modern medicine considers in this regard its main task in the curation of such patients, the maximum possible restoration of the functions of the affected brain and the volume of its control over the body. Due to the rapid development of medicine associated with the emergence of innovative technologies in the field of rehabilitation, hardware methods of rehabilitation today have gone far ahead and have in their arsenal a lot of high-tech tools. For this purpose, a search is being made for means of increasing the activity of brain cells located in the affected area. Of particular importance in this regard are the methods of rehabilitation in the early recovery period after ischemic stroke using robotic methods of mechanotherapy, one of which is the use of the Lokomat system. Among them, a prominent place is occupied by the walking training system - Lokomat, consisting of robotic orthoses and a body support device, which are combined with a treadmill. Information about the successful use of Lokomat during the rehabilitation of patients with movement disorders is still scattered, and this required their generalization and understanding. The main advantage of this system is the ability to effectively control and ensure high intensity, repeatability (reproducibility) and purposefulness of the trained movements. The convincing advantages of automated training on the Lokomat system compared to traditional rehabilitation in terms of various clinical indicators in patients with post-stroke hemiparesis have been identified. It was shown that in patients trained on the Lokomat system, a single support on the paretic leg intensified, which contributed to a more symmetrical gait. This system is more than other devices and technologies designed for learning to walk, in line with the modern approach to the restoration of impaired motor functions. The inclusion of training sessions on the Lokomat robotic system in the comprehensive treatment of patients with post-stroke hemiparesis leads to a marked improvement in movement skills. This is associated with a pronounced restructuring against the background of its use of the motor stereotype of walking, which makes it possible to increase the effectiveness of recreational activities in post-stroke patients.

scholarly journals Monocyte Chemotactic Protein-1 as a Potential Biomarker for Early Anti-Thrombotic Therapy after Ischemic Stroke

2012 ◽  
Vol 13 (7) ◽  
pp. 8670-8678 ◽  
Author(s):  
Hans Worthmann ◽  
Reinhard Dengler ◽  
Helmut Schumacher ◽  
Andreas Schwartz ◽  
Wolfgang G. Eisert ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein ◽  
Potential Biomarker

scholarly journals Transfer RNA fragments replace microRNA regulators of the cholinergic post-stroke immune blockade

2020 ◽  
Author(s):  
Katarzyna Winek ◽  
Sebastian Lobentanzer ◽  
Bettina Nadorp ◽  
Serafima Dubnov ◽  
Claudia Dames ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Immune Responses ◽  
Small Rna ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Transfer Rna ◽  
Raw 264.7 Cells ◽  
Post Stroke ◽  
Susceptibility To Infection ◽  
Rna Fragments

AbstractStroke is a leading cause of death and disability. Recovery depends on a delicate balance between inflammatory responses and immune suppression, tipping the scale between brain protection and susceptibility to infection. Peripheral cholinergic blockade of immune reactions fine-tunes this immune response, but its molecular regulators are unknown. Here, we report a regulatory shift in small RNA types in patient blood sequenced two days after ischemic stroke, comprising massive decreases of microRNA levels and concomitant increases of transfer RNA fragments (tRFs) targeting cholinergic transcripts. Electrophoresis-based size-selection followed by RT-qPCR validated the top 6 upregulated tRFs in a separate cohort of stroke patients, and independent datasets of small and long RNA sequencing pinpointed immune cell subsets pivotal to these responses, implicating CD14+ monocytes in the cholinergic inflammatory reflex. In-depth small RNA targeting analyses revealed the most-perturbed pathways following stroke and implied a structural dichotomy between microRNA and tRF target sets. Furthermore, lipopolysaccharide stimulation of murine RAW 264.7 cells and human CD14+ monocytes upregulated the top 6 stroke-perturbed tRFs, and overexpression of stroke-inducible tRF-22-WE8SPOX52 using an ssRNA mimic induced downregulation of immune regulator Z-DNA binding protein 1 (Zbp1). In summary, we identified a “changing of the guards” between RNA types that may systemically affect homeostasis in post-stroke immune responses, and pinpointed multiple affected pathways, which opens new venues for establishing therapeutics and biomarkers at the protein- and RNA-level.Significance StatementIschemic stroke triggers peripheral immunosuppression, increasing the susceptibility to post-stroke pneumonia that is linked with poor survival. The post-stroke brain initiates intensive communication with the immune system, and acetylcholine contributes to these messages; but the responsible molecules are yet unknown. We discovered a “changing of the guards,” where microRNA levels decreased but small transfer RNA fragments (tRFs) increased in post-stroke blood. This molecular switch may re-balance acetylcholine signaling in CD14+ monocytes by regulating their gene expression and modulating post-stroke immunity. Our observations point out to tRFs as molecular regulators of post-stroke immune responses that may be potential therapeutic targets.

scholarly journals Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke

2020 ◽  
Vol 21 (10) ◽  
pp. 3618 ◽  
Author(s):  
Anna Kloska ◽  
Marcelina Malinowska ◽  
Magdalena Gabig-Cimińska ◽  
Joanna Jakóbkiewicz-Banecka
Keyword(s):  
Fatty Acids ◽  
Ischemic Stroke ◽  
Brain Tissue ◽  
Lipid Mediators ◽  
Normal Brain ◽  
Stroke Treatment ◽  
Post Stroke ◽  
Increased Risk ◽  
Risk Biomarkers ◽  
And Function

Stroke is a severe neurological disorder in humans that results from an interruption of the blood supply to the brain. Worldwide, stoke affects over 100 million people each year and is the second largest contributor to disability. Dyslipidemia is a modifiable risk factor for stroke that is associated with an increased risk of the disease. Traditional and non-traditional lipid measures are proposed as biomarkers for the better detection of subclinical disease. In the central nervous system, lipids and lipid mediators are essential to sustain the normal brain tissue structure and function. Pathways leading to post-stroke brain deterioration include the metabolism of polyunsaturated fatty acids. A variety of lipid mediators are generated from fatty acids and these molecules may have either neuroprotective or neurodegenerative effects on the post-stroke brain tissue; therefore, they largely contribute to the outcome and recovery from stroke. In this review, we provide an overview of serum lipids associated with the risk of ischemic stroke. We also discuss the role of lipid mediators, with particular emphasis on eicosanoids, in the pathology of ischemic stroke. Finally, we summarize the latest research on potential targets in lipid metabolic pathways for ischemic stroke treatment and on the development of new stroke risk biomarkers for use in clinical practice.

Characterization of Near-Infrared Functional Lymphatic Imaging in the Rat Tail Model

2013 ◽  
Author(s):  
Michael Weiler ◽  
J. Brandon Dixon
Keyword(s):  
Near Infrared ◽  
Immune Cell ◽  
Imaging Modality ◽  
Lymphatic Vessels ◽  
The Body ◽  
Cell Trafficking ◽  
Nir Imaging ◽  
Lymphatic Vasculature ◽  
Rat Tail Model ◽  
Lymphatic Imaging

The lymphatic vasculature is present in nearly every tissue of the body to serve essential functions in fluid homeostasis, immune cell trafficking, and lipid transport, and it has been implicated in the progression of several diseases. Despite the critical roles that this system performs, very little is known about the lymphatic vasculature in comparison to the blood vasculature, which can be attributed, in part, to the difficulty associated with imaging lymphatic vessels. With the growing interest in studying lymphatics, near-infrared (NIR) imaging has emerged in the literature as a novel lymphatic imaging modality to simultaneously improve spatial resolution to visualize small initial lymphatics and increase temporal resolution to capture the dynamic lymphatic pump function responsible for fluid propulsion.

Engineering Tools for Studying the Interplay Between Mechanics and Biology in Lymphatic Lipid Transport

2010 ◽  
Author(s):  
J. Brandon Dixon
Keyword(s):  
Immune Cell ◽  
Mechanical Load ◽  
Contractile Function ◽  
Lymphatic Vessels ◽  
Dietary Lipid ◽  
The Body ◽  
Lipid Transport ◽  
Cell Trafficking

The lymphatic vasculature extends through most tissues of the body and plays an essential role in maintaining fluid balance, immune cell trafficking, and lipid transport. Nearly all dietary lipid is transported from the intestine to the circulation via the lymphatic system in the form of triglyceride-rich lipoproteins called chylomicrons. This process can be described through two different mechanisms: 1) entry of the chylomicron into the initial lymphatic vessels of the small intestine, known as lacteals, and 2) the transport of these chylomicrons through the larger collecting lymphatics by a complex and coordinated system of individual contracting vessel units (lymphangions) and valve leaflets. We describe here a set of in vitro and in vivo tools we have developed to study the mechanisms that modulate lipid transport under these two different paradigms and show how these tools are uncovering important biological features involved in these mechanisms. Lymphatic pump function is known to be sensitive to the mechanical load on the vessel as the contractility of isolated vessels has been shown to be both shear and stretch sensitive [1], yet whether these mechanisms are important in regulating contractile function in vivo remains uncertain.

scholarly journals Sustained Increases in Immune Transcripts and Immune Cell Trafficking During the Recovery of Experimental Brain Ischemia

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2514-2525 ◽  
Author(s):  
Wen Fury ◽  
Keun Woo Park ◽  
Zhuhao Wu ◽  
Eunhee Kim ◽  
Moon-sook Woo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Immune Cells ◽  
Fluorescent Protein ◽  
Immune Cell ◽  
Chronic Phase ◽  
Mononuclear Phagocytes ◽  
Multiple Time ◽  
Immune Gene ◽  
Cell Trafficking ◽  
Time Points

Background and Purpose: Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months. Methods: Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain imaging was performed in asplenic mice receiving GFP + (green fluorescent protein)-tagged splenocytes. Results: Sustained stroke-induced mRNA abundance changes were observed in both hemispheres with 2989 ipsilateral and 822 contralateral genes significantly perturbed. In the hemisphere ipsilateral to the infarct, genes associated with immune functions were strongly affected, including temporally overlapping innate and adaptive immunity and macrophage M1 and M2 phenotype-related genes. The strong immune gene activation was accompanied by the sustained infiltration of peripheral immune cells at acute, subacute, and recovery stages of stroke. The infiltrated immune cells were found in the infarcted area but also in remote regions at 2 months after stroke. Conclusions: The study identifies that immune components are the predominant molecular signatures and they may propagate or continuously respond to brain injury in the subacute to chronic phase after central nervous system injury. The study suggests a potential immune-based strategy to modify injury progression and tissue remodeling in ischemic stroke, even months after the initiating event.

Abstract 12650: Activity of Serum Angiotensin Converting Enzyme 2 is Decreased During Acute Ischemic Stroke in Humans

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Douglas M Bennion ◽  
Christian A Rosado ◽  
Emily H Haltigan ◽  
Colin Sumners ◽  
Michael F Waters
Keyword(s):  
Enzyme Activity ◽  
Ischemic Stroke ◽  
Angiotensin Converting Enzyme ◽  
Acute Ischemic Stroke ◽  
Converting Enzyme ◽  
Serum Samples ◽  
Necrosis Factor Alpha ◽  
Angiotensin Converting Enzyme 2 ◽  
Post Stroke ◽  
Rebound Increase

Introduction: The expression and activity of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase, has recently been shown to be dynamically altered during and after stroke in animal models. Hypothesis: The aim of this study was to characterize the previously unexplored changes in activity of ACE2 in the serum of patients experiencing acute ischemic stroke. Methods: Serum samples were obtained from patients presenting with acute ischemic stroke (n=20) and again at three days post-stroke and enzyme activity levels were analyzed by fluorometric assay and compared to levels from non-stroke control patients (n=20). Results: Ischemic stroke resulted in a significant decrease in serum ACE2 at an average of 3.5 hours after stroke, which was followed by a rebound increase by three days later (Fig 1). ACE activity was also significantly decreased following stroke, but without rebound increases. Tumor necrosis factor-alpha converting enzyme activity was not significantly different from control. ACE2 activity was negatively correlated with systolic blood pressure (SBP) among stroke patients (Fig 2), while activity was positively correlated with SBP among a cohort of healthy young adults (n=16). Conclusions: The characterization of the dynamic and novel changes in serum ACE2 activity in human stroke, which follow observations from preclinical studies, along with the demonstration of a negative association with SBP, provides new insight for the development of therapies that target this protective system in the context of ischemic stroke. Data are mean ± SEM. RFU: relative fluorescence units; *p<0.001 vs. control; †p<0.05 vs. 4h post stroke.

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