Multiple sclerosis is an autoimmune disease of the central nervous system characterized by neuroinflammation and demyelination. Although considered a T cell-mediated disease, multiple sclerosis involves the activation of both adaptive and innate immune cells, as well as resident cells of the central nervous system, which synergize in inducing inflammation and thereby demyelination. Differentiation, survival, and inflammatory functions of innate immune cells and of astrocytes of the central nervous system are regulated by tyrosine kinases. Here, we show that imatinib, sorafenib, and GW2580—small molecule tyrosine kinase inhibitors can each—prevent the development of disease and treat established disease in a mouse model of multiple sclerosis. In vitro, imatinib and sorafenib inhibited astrocyte proliferation mediated by the tyrosine kinase platelet-derived growth factor receptor (PDGFR), whereas GW2580 and sorafenib inhibited macrophage tumor necrosis factor (TNF) production mediated by the tyrosine kinases c-Fms and PDGFR, respectively. In vivo, amelioration of disease by GW2580 was associated with a reduction in the proportion of macrophages and T cells in the CNS infiltrate, as well as a reduction in the levels of circulating TNF. Our findings suggest that GW2580 and the FDA-approved drugs imatinib and sorafenib have potential as novel therapeutics for the treatment of autoimmune demyelinating disease.

Background: Indirect blood pressure measurements are often used to guide clinical decisions, but few studies have verified their agreement with direct arterial blood pressure in nonhuman primates. Here, the accuracy and precision of Doppler (DOP) and oscillometric (OS) [systolic (OSsys), mean (OSmean), and diastolic (OSdias)] blood pressure readings were assessed in rhesus macaques.Methods: DOP and OS were utilized to measure blood pressure values in nine anesthetized rhesus macaques, which were compared to direct measurements via a saphenous arterial catheter. All measurements were taken simultaneously every 5 min for 60-240 min.Results: DOP and OSsys underestimated direct systolic arterial pressure with a bias ± precision of 10.21 ± 6.37 mmHg and 11.67 ± 11.55 mmHg, respectively. OSmean correlated well with direct mean arterial pressure with a bias ± precision of 7.25 ± 7.35 mmHg. Conclusions: DOP provided the better representation of systolic blood pressure, andOSmean provided a useful representation of mean arterial pressure in anesthetized rhesus macaques. K E Y W O R D Sindirect blood pressure, nonhuman primate, non-invasive blood pressure

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