Significance The pore-forming protein gasdermin D (GSDMD) was recently identified as the principal executioner of pyroptosis (“fiery death”), a type proinflammatory programmed cell death driven by inflammasomes. Caspase-1 cleaves GSDMD, but whether this process contributes to neuroinflammation is unknown. Here, we report evidence GSDMD-mediated primary mechanism inflammatory demyelination in central nervous system during multiple sclerosis (MS), debilitating and incurable demyelinating...

MicroRNAs have emerged as an important class of modulators gene expression. These molecules influence protein synthesis through translational repression or degradation mRNA transcripts. Herein, we investigated the potential role miR-142a isoforms, miR-142a-3p and miR-142a-5p, in context autoimmune neuroinflammation.The expression levels two mature isoforms miR-142 were measured brains patients with multiple sclerosis (MS) CNS tissues from mice experimental encephalomyelitis (EAE), animal...

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Neurosteroids are reported to exert anti‐inflammatory effects in several neurological disorders. We investigated expression and actions neurosteroid, dehydroepiandrosterone (DHEA), its more stable 3β‐sulphated ester, DHEA‐S, MS associated experimental models. CNS tissues from patients with animals autoimmune encephalomyelitis (EAE) displayed reduced DHEA concentrations, accompanied...

Preventing immune cells from invading sites of brain injury facilitates repair damaged blood vessels in diabetic mice.

Vascular pathology is associated with cognitive impairment in diseases such as type 1 diabetes; however, how capillary flow affected and the underlying mechanisms remain elusive. Here we show that capillaries diabetic mouse brain both sexes are prone to stalling, blocks consisting primarily of erythrocytes branches off ascending venules. Screening for circulating inflammatory cytokines revealed persistently high levels interleukin-10 (IL-10) mice. Contrary expectation, stimulating IL-10...

Although microglia possess the unique ability to migrate, whether mobility is evident in all microglia, sex dependent, and what molecular mechanisms drive this, not well understood adult brain. Using longitudinal vivo two-photon imaging of sparsely labeled we find a relatively small population (~5%) are mobile under normal conditions. Following injury (microbleed), fraction increased sex-dependent manner, with male migrating significantly greater distances toward microbleed relative their...

Background and Purpose: Thrombolysis can improve outcome in patients with acute ischemic stroke. However, recanalization is not always complete persisting cerebral vascular occlusion >50% of despite treatment. Properties the formed thrombus may influence thrombolysis efficiency impede success. Here we examine whether differences thrombin generation are associated unfavourable treated Methods: Two cohorts stroke were recruited (cohort 1 n=36 patients, cohort 2 n= 42). Thrombin was...

Introduction: Senescent cells accumulate with advancing age, and exposure to cellular stressors, such as oxidative inflammatory molecules, which can be circulating in blood. endothelial have altered functions that may influence stroke outcomes. Studying senescence might reveal improved strategies improve vascular health prevent or better Hypothesis: Acute ischemic patients enriched gene set expression worse 90-day Methods: In 225 acute stroke, RNA was isolated from whole blood transcriptome...

Abstract Stroke profoundly disrupts cortical excitability which impedes recovery, but how it affects the function of specific inhibitory interneurons, or subpopulations therein, is poorly understood. Interneurons expressing vasoactive intestinal peptide (VIP) represent an intriguing stroke target because they can regulate through disinhibition. Here we chemogenetically augmented VIP interneuron in a murine model photothrombotic and show that enhances somatosensory responses improves recovery...

Abstract Vascular pathology is associated with cognitive impairment in diseases such as type 1 diabetes, but precisely how capillary flow affected and the underlying mechanisms remain elusive. Here we show that capillaries diabetic mouse brain are prone to stalling, blocks composed primarily of erythrocyte plugs branches off penetrating venules. Increased obstructions were evident both sexes only partially reversed by insulin. Screening for circulating inflammatory cytokines revealed...

Dendritic cells (DCs) play a crucial role in the initiation of adaptive immune responses against tumor cells. We recently found that protein components Toxoplasma gondii (T. gondii) could mature DCs efficiently. Therefore, this study, we aimed to find most effective T. which are able and consequently instruct tumor-bearing mice. Soluble tachyzoite antigens (STAgs) were fractionated by ammonium sulfate precipitation subsequently anion-exchange HPLC. Immature (iDCs) treated these fractions...

Background and Purpose: Sex differences in stroke exist, including variation risk outcome. Differences thrombin generation may contribute to this between females males. To examine this, we assessed sex males with acute ischemic the relationship blood cell gene expression. Methods: In 97 patients was measured by assay. Blood expression microarray. sexes were identified examined. Genes associated analysed functional pathway analysis. Results: Females had similar overall capacity generate...

Mechanisms underlying the systemic lupus erythematosus (SLE) have not yet been elucidated. In this study, we evaluated balance of T cell subsets in BALB/c mice model SLE induced; using Con A and polyamines as DNA immunogenicity modifiers. were immunized subcutaneously with 50 µg extracted from cells cultured different conditions: splenocytes+ (group P), A), polyamines+ PA) splenocytes only (control). Anti-double-stranded -(ds-DNA) antibodies, proteinuria, antinuclear autoantibodies assessed...

Abstract Background: DCs based immunotherapy is considered as a promising approach for activating immune responses against tumor antigens. It has been believed that TLR ligands derived from microorganisms are more potent in DCs. In this study, the effects of Toxoplasma gondii (T.gondii) protein and DNA components on human maturation were evaluated. Method: T.gondii Tachyzoites obtained by intraperitoneal passage mice. Protein extracted relevant kits. Subsequently, lysate was fractionated...

Event Abstract Back to Toxoplasma gondii protein fractions for the generation of dendritic cell based cancer vaccine Roobina Boghozian1, Azad Saei1, Reza Mirzaei1 and Jamshid Hadjati1* 1 Terhran University Medical Sciences, Iran Dendritic (DC) immunotherapy appears be a promising approach successfully induce an antitumor immune response. Therefore, DC vaccines frequently used in many therapy protocols. DCs are most potent antigenpresenting cells up on maturation with different stimulators...

Abstract Dendritic cells (DCs) are professional antigen presenting that both initiate and modulate the immune responses. DCs activation leads to their maturation production of cytokines such as IL-12. Therefore, use in immunotherapy against cancers has been studied. We have investigated potency Toxoplasma gondii (TG) proteins for DC induce IL-12 mouse spleen cell proliferation. Methods: were generated from Balb/c bone marrow presence GM-CSF IL-4. Four protein fractions obtained sonically...