Direct Angiotensin At2-Receptor Stimulation Improves Survival and Neurological Outcome in Experimental Stroke (Mcao) in Mice

Schwengel, Katja; Thöne-Reineke, Christa; Lucht, Kristin; Namsolleck, Pawel; Müller, S.; Horiuchi, Masatsugu; Iwai, Masaru; Dahlöf, Björn; Hallberg, Anders; Unger, Th.; Steckelings, U. Muscha

doi:10.1097/00004872-201106001-00123

Cited by 4 publications

(2 citation statements)

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“…Furthermore, several in vivo studies by others and us have shown that the doses for C21 used in our study are AT 2 R-specific in vivo [30,55,56]. However, we provide in vitro evidence that all major protective effects of C21 were AT 2 R-mediated and could be inhibited by an AT 2 R antagonist.…”

Section: Limitationsmentioning

confidence: 51%

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice

et al. 2014

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In the present study, we evaluated stimulation of the angiotensin type 2 receptor (AT2R) by the selective non-peptide agonist Compound 21 (C21) as a novel therapeutic concept for the treatment of multiple sclerosis using the model of experimental autoimmune encephalomyelitis (EAE) in mice. C57BL-6 mice were immunized with myelin-oligodendrocyte peptide and treated for 4 weeks with C21 (0.3 mg/kg/day i.p.). Potential effects on myelination, microglia and T-cell composition were estimated by immunostaining and FACS analyses of lumbar spinal cords. The in vivo study was complemented by experiments in aggregating brain cell cultures and microglia in vitro. In the EAE model, treatment with C21 ameliorated microglia activation and decreased the number of total T-cells and CD4+ T-cells in the spinal cord. Fluorescent myelin staining of spinal cords further revealed a significant reduction in EAE-induced demyelinated areas in lumbar spinal cord tissue after AT2R stimulation. C21-treated mice had a significantly better neurological score than vehicle-treated controls. In aggregating brain cell cultures challenged with lipopolysaccharide (LPS) plus interferon-γ (IFNγ), AT2R stimulation prevented demyelination, accelerated re-myelination and reduced the number of microglia. Cytokine synthesis and nitric oxide production by microglia in vitro were significantly reduced after C21 treatment. These results suggest that AT2R stimulation protects the myelin sheaths in autoimmune central nervous system inflammation by inhibiting the T-cell response and microglia activation. Our findings identify the AT2R as a potential new pharmacological target for demyelinating diseases such as multiple sclerosis.

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Section: Limitationsmentioning

confidence: 51%

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice

et al. 2014

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“…After stroke, for instance, regions surrounding infarcted tissue demonstrate increased neurogenesis, allowing for behavior-driven plasticity during recovery. 37 38 These changes are driven by several mechanisms, such as enhanced neuronal activity in peri-infarct tissue, 39 angiogenesis, 40 expression of growth factors, 41 42 and suppression of apoptosis. 43 Social stimulation has been shown to enhance these neuroplastic processes in normal and brain-damaged animals.…”

Section: Biological Importance Of Social Connectionmentioning

confidence: 99%

Leveraging Social Networks for the Assessment and Management of Neurological Patients

et al. 2022

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Social networks are the persons surrounding a patient who provide support, circulate information, and influence health behaviors. For patients seen by neurologists, social networks are one of the most proximate social determinants of health that are actually accessible to clinicians, compared with wider social forces such as structural inequalities. We can measure social networks and related phenomena of social connection using a growing set of scalable and quantitative tools increasing familiarity with social network effects and mechanisms. This scientific approach is built on decades of neurobiological and psychological research highlighting the impact of the social environment on physical and mental well-being, nervous system structure, and neuro-recovery. Here, we review the biology and psychology of social networks, assessment methods including novel social sensors, and the design of network interventions and social therapeutics.

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AT2 Receptor and Tissue Injury: Therapeutic Implications

et al. 2014

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The renin-angiotensin system (RAS) plays an important role in the initiation and progression of tissue injuries in the cardiovascular and nervous systems. The detrimental actions of the AT1 receptor (AT1R) in hypertension and vascular injury, myocardial infarction and brain ischemia are well established. In the past twenty years, protective actions of the RAS, not only in the cardiovascular, but also in the nervous system, have been demonstrated. The so-called protective arm of the RAS includes AT2-receptors and Mas receptors (AT2R and MasR) and is characterized by effects different from and often opposing those of the AT1R. These include anti-inflammation, anti-fibrosis, anti-apoptosis and neuroregeneration that can counterbalance pathological processes and enable recovery from disease. The recent development of novel, small-molecule AT2R agonists offers a therapeutic potential in humans with a variety of clinical indications.

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Direct Angiotensin At2-Receptor Stimulation Improves Survival and Neurological Outcome in Experimental Stroke (Mcao) in Mice

Cited by 4 publications

References 0 publications

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice

Leveraging Social Networks for the Assessment and Management of Neurological Patients

AT2 Receptor and Tissue Injury: Therapeutic Implications

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