Collectively, our findings implicate that P-gp inhibitor can promote the therapeutic efficacy of ASIV on EAE mice, which may boost its clinical usage together with ASIV in the therapy of MS.
In the present study, we found for the first time that ASIV induced the upregulation of P-gp and BCRP in the central nervous system (CNS) microvascular endothelial cells of EAE mice.
Both inhibitors failed to improve corticospinal tract conduction latency and to attenuate inflammation at EAE recovery phase, despite being equally active at targeting brain ABHD6.
The presence of a single nucleotide polymorphism causing an amino acid change in a near actin-interacting domain of Arg, in addition to altered lymphocyte activation in the congenic mice upon immunization with myelin antigen, makes Abl2/Arg a candidate gene for EAE.
Increased activity of angiotensin-converting enzyme (ACE) in the blood and cerebrospinal fluid of patients with multiple sclerosis (MS), and the inhibition of ACE in experimental autoimmune encephalomyelitis, suggested that ACE may play a role in the pathogenesis and progression of MS. We recently published the first report on the potential association of MS and ACE I/D polymorphism in Slovenian and Croatian patients with MS, in which it was shown that the DD genotype might contribute to a higher risk of developing MS in men.
Published research has described increased expression of AT1R and ACE in tissues from MS patients and in animal models of MS such as experimental autoimmune encephalomyelitis (EAE).
Taken together, our data show a role for erythrocyte DARC as a chemokine reservoir and that endothelial DARC contributes to the pathogenesis of experimental autoimmune encephalomyelitis by shuttling chemokines across the blood-brain barrier.
Altogether, our data elucidate the mechanism of dexmedetomidine-induced CXCR7 desensitization in microglia and amelioration in EAE, which might lead to a better understanding of the therapeutic effects of dexmedetomidine as well as its implications for CXCR7 desensitization in autoimmune disease.
Contrasting the situation in the intact CNS, a striking increase in astrocytic CXCR7 expression was detectable in the cortex of rats with experimental brain infarcts, in the spinal cord of rats with experimental autoimmune encephalomyelitis (EAE) and after mechanical compression, as well as in the in infarcted human cerebral cortex and in the hippocampus of Alzheimer's disease patients.
Here we demonstrate that the non-synonymous SNP does not change Arg's binding affinity for F-actin but suggest a role for Abl kinases in CNS inflammation pathogenesis by showing that pharmacological inhibition of Abl kinases ameliorates EAE, but not experimental arthritis.
In contrast to our previous EAE studies using PACAP global knockout mice which developed severe and prolonged EAE, we found that mice with conditional loss of PAC1 receptors in catecholaminergic cells developed a delayed time course of EAE with reduced helper T cell type 1 (Th1) and Th17 and enhanced Th2 cell polarization.
In contrast to our previous EAE studies using PACAP global knockout mice which developed severe and prolonged EAE, we found that mice with conditional loss of PAC1 receptors in catecholaminergic cells developed a delayed time course of EAE with reduced helper T cell type 1 (Th1) and Th17 and enhanced Th2 cell polarization.
Taken together, our results show that Gpr97 plays an important role in the development of EAE and may have a therapeutic potential for the treatment of CNS autoimmunity.
In this study, we report that dexmedetomidine, an alpha 2a adrenergic receptor agonist, attenuates the clinical severity of EAE with less infiltration of microglia.
β2-Adrenergic receptor (Adrb2) signaling limits T cell autoimmunity in EAE through a mechanism mediated by the suppression of IL-2, IFN-γ, and GM-CSF production via inducible cAMP early repressor (ICER).
In MS, several reports have suggested that restricted T-cell populations respond to MPB, as in inbred rodents with the MS disease model experimental allergic encephalomyelitis.