Ischemic stroke is a leading cause of death and disability in the United States. It is known that males and females respond differently to stroke. Depending on age, the incidence, prevalence, mortality rate, and disability outcome of stroke differ between the sexes.
View Article and Find Full Text PDFPeroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor transcription factor that plays a role in immune regulation. Because of its expression in cerebral tissue and immune cells, PPARα has been examined as an important regulator in immune-based neurological diseases. Many studies have indicated that pre-treatment of animals with PPARα agonists induces protection against stroke.
View Article and Find Full Text PDFThe peripheral immune response contributes to neurologic impairment after stroke and the extent of initial damage is greater in males than females. We have previously shown that spleen cells directly contribute to ischemic damage in males, as splenectomy prior to experimental stroke eliminates the sex differences in infarct volume. This study aims to determine which specific subset of immune cells exert pathogenic effects when injected 24 hours before MCAO induction into splenectomized male and female WT mice.
View Article and Find Full Text PDFInflammation and thrombosis are tightly linked, with inflammation contributing to thromboembolism and to stroke outcome. Thromboembolism is a frequent cause of ischemic stroke; yet, the most used occlusion mouse models of experimental stroke do not effectively replicate thromboembolism. Our group recently described a novel thromboembolic mouse model of stroke that successfully occludes the middle cerebral artery with high reproducibility.
View Article and Find Full Text PDFMales and females respond differently to stroke. Moreover, females often experience worse long-term stroke outcomes. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist has been shown to improve stroke outcome and resolve neuroinflammation in male mice.
View Article and Find Full Text PDFBackground And Purpose: Both pathogenic and regulatory immune processes are involved in the middle cerebral artery occlusion (MCAO) model of experimental stroke, including interactions involving the programmed death 1 (PD-1) receptor and its 2 ligands, PD-L1 and PD-L2. Although PD-1 reduced stroke severity, PD-L1 and PD-L2 appeared to play pathogenic roles, suggesting the use of anti-PD-L monoclonal antibody therapy for MCAO.
Methods: Male C57BL/6 mice were treated with a single dose of anti-PD-L1 monoclonal antibody 4 hours after MCAO and evaluated for clinical, histological and immunologic changes after 96 hours of reperfusion.
The peripheral immune response contributes to neurodegeneration after stroke yet little is known about how this process differs between males and females. The current study demonstrates that splenectomy prior to experimental stroke eliminates sex differences in infarct volume and activated brain monocytes/microglia. In the periphery of both sexes, activated T cells correlate directly with stroke outcome while monocytes are reduced by splenectomy only in males.
View Article and Find Full Text PDFStroke is a leading cause of death and disability in the United States. The lack of clinical success in stroke therapies can be attributed, in part, to inadequate basic research on aging rodents. The current study demonstrates that recombinant TCR ligand therapy uses different immunological mechanisms to protect young and older mice from experimental stroke.
View Article and Find Full Text PDFClin Transl Allergy
September 2013
Background: Omalizumab, is a humanized anti-IgE monoclonal antibody used to treat allergic asthma. Decreased serum IgE levels, lower eosinophil and B cell counts have been noted as a result of treatment. In vitro studies and animal models support the hypothesis that omalizumab inhibits IgE synthesis by B cells and causes elimination of IgE-expressing cells either by induction of apoptosis or induction of anergy or tolerance.
View Article and Find Full Text PDFIn insulin dependent diabetes mellitus (T1D), self-reactive T cells infiltrate pancreatic islets and induce beta cell destruction and dysregulation of blood glucose. A goal is to control only the self-reactive T cells, leaving the remainder of the T cell population free to protect the host. One approach is blockade of the second signal for T cell activation while allowing the first (antigen-specific) signal to occur.
View Article and Find Full Text PDFType 1 diabetes (T1D) is characterized by hyperglycemia due to lost or damaged islet insulin-producing β -cells. Rodent models of T1D result in hyperglycemia, but with different forms of islet deterioration. This study focused on 1 toxin-induced and 2 autoimmune rodent models of T1D: BioBreeding Diabetes Resistant rats, nonobese diabetic mice, and Dark Agouti rats treated with streptozotocin.
View Article and Find Full Text PDFWith antigen stimulation, naïve CD4+ T cells differentiate to several effector or memory cell populations, and cytokines contribute to differentiation outcome. Several proteins on these cells receive costimulatory signals, but a systematic comparison of their differential effects on naïve T cell differentiation has not been conducted. Two costimulatory proteins, CD28 and ICAM-1, resident on human naïve CD4+ T cells were compared for participation in differentiation.
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