USP18 Overexpression Protects against Focal Cerebral Ischemia Injury in Mice by Suppressing Microglial Activation

This study aims to determine whether USP18 expression protects against brain damage in ischemic models of stroke. We investigated USP18 expression, overexpression, and knockout under ischemic conditions in vitro and in vivo. Using BV2 microglial cells under oxygen and glucose deprivation (OGD) and 60 min transient middle cerebral artery occlusion (MCAO) in mice as models of ischemia, we assessed the infarct volume, the extent of neurogenesis, the expression of proinflammatory cytokines and Janus Kinases (JAKs)/Signal Transducer and Activator of Transcription (STAT) pathway members. BV2 cells under OGD for 0, 6, 12, or 24 hours exhibited decreased USP18 expression and increased expression of the proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and interferon (INF)-γ. Lentiviral overexpression of USP18 in MCAO mice significantly decreased the infarct volume and significantly increased the number of new neurons that coexpressed bromodeoxyuridine (BrdU)/ neuronal nuclei (NeuN). Additionally, microglial activation was inhibited, including the suppression of the JAK/STAT pathway and the proinflammatory cytokines expression. In vitro experiments demonstrated that USP18 inhibited BV2 microglial activity and reduced the mRNA and protein levels of NF-κB, JAK1, p-JAK1, STAT1, and p-STAT1 in BV2 microglial cells. USP18 overexpression decreased ischemic brain injury through the suppression of microglial activation b...
Source: Neuroscience - Category: Neuroscience Source Type: research

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In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
AbstractGadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and resea...
Source: Insights into Imaging - Category: Radiology Source Type: research
AbstractPurpose of ReviewTo review the latest information about the interactions between cancer and cerebrovascular disease.Recent FindingsAdditional data support the finding that both ischemic and hemorrhagic stroke are important complications of cancer or its treatment. Reperfusion therapy is being given successfully to patients with stroke complicating cancer.SummaryHemorrhagic stroke may occur with metastatic disease to the brain, coagulopathies from cancer, in particular leukemia, or as complications of chemotherapy. Ischemic stroke also may be a complication of metastatic disease with local invasion of vessels, a pro...
Source: Current Neurology and Neuroscience Reports - Category: Neuroscience Source Type: research
The neutrophil ‐to‐lymphocyte ratio (NLR) has been shown to be a marker associated with inflammation and is independently associated with the adverse clinical outcomes of symptomatic intracranial hemorrhage, cancer, and cardiovascular disease. Our results show higher NLR can predict hemorrhagic transformation and 3‐month mortality in patients with acute ischemic stroke. AbstractIntroductionThe neutrophil ‐to‐lymphocyte ratio (NLR) has been shown to be a marker associated with inflammation and is independently associated with the adverse clinical outcomes of symptomatic intracranial hemorrhage, cancer, and cardiov...
Source: Brain and Behavior - Category: Neurology Authors: Tags: ORIGINAL RESEARCH Source Type: research
We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Purpose: The present study was to observe the therapeutic efficiency of Clematichinenoside (AR) on cerebral ischemic injury in rats, especially on neurological and motor function recovery and to explore the underlying mechanism. Methods: Following middle cerebral artery occlusion/reperfusion (MCAO/R) surgery, rats were treated orally with 32, 16, and 8 mg/kg AR respectively for 14 days during which cerebral injury was evaluated and proinflammatory factors tumor necrosis factor- α and interleukin-6 as well as neurotrophic factors brain-derived neurotrophic factor and Neurotrophin-3 levels were determined with ELISA kits.
Source: Journal of Stroke and Cerebrovascular Diseases - Category: Neurology Authors: Source Type: research
Authors: Lasek-Bal A, Jedrzejowska-Szypulka H, Student S, Warsz-Wianecka A, Zareba K, Puz P, Bal W, Pawletko K, Lewin-Kowalik J Abstract Acute cerebral ischemia triggers local and systemic immune response. The aims of this project was to assess the blood serum concentration of the markers of inflammation and markers of the blood brain barrier damage on the first day of ischemic stroke, and the mutual correlations between these marker levels. Patients with first-in-life stroke were analysed according to: plasma concentration of the following markers on the first day of stroke: interleukin 2 (IL-2) and interleuki 6 (...
Source: Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research
Abstract Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/β-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes o...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine (approval No. BUCM-3-2016040201-2003) in April 2016. PMID: 31290452 [PubMed]
Source: Cell Research - Category: Cytology Authors: Tags: Neural Regen Res Source Type: research
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