Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An orally active leukocyte recruitment inhibitor, NPC 16570 (N-[9H-fluoren-9-ylethoxycarbonyl]-4-aminobenzoic acid), was evaluated in experimental allergic encephalomyelitis (EAE) in rats. The mean time of disease onset in control animals was 12 +/- 1 days, with peak average clinical scores of 2.5 +/- 0.2, accompanied by perivascular infiltration of inflammatory cells into the CNS. Daily administration (p.o.) of NPC 16570 reduced the clinical severity (by 70%) at 10 and 30 mg/kg, and at 100 mg/kg, no clinical symptoms were detected. When NPC 16570 (100 mg/kg) treatment was initiated 7 days after EAE induction, the severity (75% inhibition) and duration of the disease were attenuated; 2 out of 6 animals showed no overt clinical symptoms and perivascular cell infiltration was prevented, suggesting potential utility in autoimmune diseases.
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PMID:Prevention and suppression of experimental allergic encephalomyelitis by an orally active leukocyte recruitment inhibitor, NPC 16570. 827 95

We have recently shown that the inflammatory process during experimental allergic encephalomyelitis (EAE), the animal model of MS, attracts transplanted NPC migration into the inflamed white matter. Here we studied how the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) affect NPC growth, survival, differentiation, and migration. Newborn rat striatal NPCs were expanded in spheres as nestin+, PSA-NCAM+, NG2(-) cells, which differentiated into astrocytes, oligodendrocytes, and neurons. NPCs expressed receptors of TNFalpha and IFNgamma but not interleukin-1. TNFalpha and IFNgamma inhibited sphere cell proliferation, determined by [(3)H]thymidine and BrdU incorporation. IFNgamma increased apoptotic cell death (determined by TUNEL stains); this effect partially blocked by TNFalpha. Neither cytokine affected NPC lineage fate, determined by percentage of GFAP+, neurofilament+, and GalC+ cells after differentiation. TNFalpha and IFNgamma increased outward migration of cells from spheres in vitro. Thus, TNFalpha and IFNgamma, key players in MS and EAE, inhibit NPC proliferation and induce their migration.
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PMID:Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells. 1466 13

Intravenous neural precursor cell (NPCs) injection attenuates experimental autoimmune encephalomyelitis by reducing autoreactive T cell encephalitogenicity in lymph nodes in vivo. Here we examined NPC-lymphocyte interactions in vitro. NPCs inhibited the induction of T cell activation marker IL-2-Receptor alpha, ICOS, PD-1 and CTLA-4 and inhibited T cell proliferation. NPCs inhibited T cell activation and proliferation in response to Concavalin-A and to anti-CD3/anti-CD28, which are T cell receptor (TCR)-mediated stimuli, but not in response to phorbol myristate acetate/ionomycin, a TCR-independent stimulus. The suppressive effect was not mediated via downregulation of CD3epsilon or induction of apoptosis. We next examined NPCs effects on inflammatory-cytokine signaling. NPCs impaired IL-2-mediated phosphorylation of JAK3 in lymphocytes, and inhibited IL-6 mediated proliferation of B9 murine hybridoma cells. In conclusion, NPCs ameliorate TCR-mediated T cell activation and inhibit inflammatory cytokines' signaling in immune cells. These findings may underlie the broad anti-inflammatory effects of NPCs in vivo.
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PMID:Neural precursor cells inhibit multiple inflammatory signals. 1869 38

It has been reported that autoimmune inflammatory processes in human multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), may induce an alteration in neurogenesis. Studies with transgenic EAE mice have demonstrated an enhancement of neurogenesis in the subventricular zone (SVZ). In contrast, a reduction of stem cell proliferation in the same region has been observed by Pluchino et al. [Brain 2008;131:2564-2578] in myelin oligodendrocyte glycoprotein (MOG)-induced EAE mice. We immunized female C57BL/6 mice with MOG 35-55 peptide and successfully developed chronic/nonremitting EAE, which is believed to be analogous to the progressive form of MS. On day 21 postimmunization, coronal brain sections were collected and stained with anti-5-bromo-2'-deoxyuridine (BrdU) antibody. By counting the number of BrdU-labeled cells, we demonstrated that the neural stem/progenitor cell (NSC/NPC) proliferation decreased in the SVZ, which basically confirms the study of Pluchino et al. on the changes in the SVZ. A reduction of NSC/NPC proliferation also occurred in the hippocampal subgranular zone of the dentate gyrus. The hippocampus is well known to be an important region involved in learning and memory; thus, our finding may offer a possible explanation for the cognitive impairment in human chronic MS.
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PMID:Decreased neural stem/progenitor cell proliferation in mice with chronic/nonremitting experimental autoimmune encephalomyelitis. 1978 10

Postnatally isolated neural precursor cells (piNPCs) from mouse cerebral tissue have been studied in cell-based therapeutic approaches for Experimental Autoimmune Encephalomyelitis (EAE). Transplantation experiments in EAE rodents revealed that piNPCs manage to integrate into the host tissue and ameliorate clinical symptoms. When cultured in vitro, mouse cerebral piNPCs form neurospheres consisting of immature cells positive for polysialylated neural adhesion molecule (PSA-NCAM) that differentiate mainly towards glial cells, but also neurons. Herein, we have characterized piNPCs immunophenotype, with flow cytometry. NPCs were positive for CD24, CD44, and CD133 though negative for CD15, CD184 and CD49d. This immunophenotype, determined for the first time, among cells isolated from neonates might be useful for the identification of NPC population aiming at the development of transplantation protocols.
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PMID:Immunophenotype of mouse cerebral hemispheres-derived neural precursor cells. 2659 Mar 29

Multiple sclerosis (MS) is a chronic, inflammatory autoimmune disease that affects the central nervous system (CNS) for which there is no cure. In MS, encephalitogenic T cells infiltrate the CNS causing demyelination and neuroinflammation; however, little is known about the role of regulatory T cells (Tregs) in CNS tissue repair. Transplantation of neural stem and progenitor cells (NSCs and NPCs) is a promising therapeutic strategy to promote repair through cell replacement, although recent findings suggest transplanted NSCs also instruct endogenous repair mechanisms. We have recently described that dampened neuroinflammation and increased remyelination is correlated with emergence of Tregs following human NPC transplantation in a murine viral model of immune-mediated demyelination. In the current study we utilized the prototypic murine autoimmune model of demyelination experimental autoimmune encephalomyelitis (EAE) to test the efficacy of hNSC transplantation. Eight-week-old, male EAE mice receiving an intraspinal transplant of hNSCs during the chronic phase of disease displayed remyelination, dampened neuroinflammation, and an increase in CNS CD4+CD25+FoxP3+ regulatory T cells (Tregs). Importantly, ablation of Tregs abrogated histopathological improvement. Tregs are essential for maintenance of T cell homeostasis and prevention of autoimmunity, and an emerging role for Tregs in maintenance of tissue homeostasis through interactions with stem and progenitor cells has recently been suggested. The data presented here provide direct evidence for collaboration between CNS Tregs and hNSCs promoting remyelination.
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PMID:Regulatory T cells promote remyelination in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis following human neural stem cell transplant. 3227 10