myelin-basic-protein and montelukast

The main pathological characteristics of demyelinating diseases are central nervous system (CNS) myelin damage, and the differentiation of oligodendrocyte precursor cells is the therapeutic target of myelin repair. Previous studies have found that a large number of platelet-derived growth factor receptor α(PDGFRα) positive oligodendrocyte progenitor cells (OPCs) accumulate in the lesion area of myelin injury, and differentiation is blocked. However, the therapeutic effects of drugs currently used clinically on OPCs differentiation and myelin repair are limited. The main reason is that it is difficult to reach the effective concentration of the drug in the lesion area. Therefore, efficiently delivering into the CNS lesion area is of great significance for the treatment of MS. Natural exosomes have good biocompatibility and are ideal drug carriers. The delivery of drugs to lesion areas can be achieved by giving the exosomes armed targeting ligand. Therefore, in this study, combining exosomes with PDGFA helps them accumulate in OPCs in vitro and in vivo. Further, load montelukast into exosomes to achieve targeted therapy for cuprizone-induced demyelination animal model. The implementation of this research will help provide effective treatments for demyelinating diseases and lay a theoretical foundation for its application in the clinical treatment of different demyelinating diseases.

Topics: Acetates; Animals; Cell Differentiation; Cell Lineage; Cuprizone; Cyclopropanes; Demyelinating Diseases; Disease Models, Animal; Drug Delivery Systems; Exosomes; Extracellular Vesicles; In Vitro Techniques; Ligands; Male; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Myelin Sheath; Neurons; Oligodendrocyte Precursor Cells; Oligodendroglia; Phagocytosis; Quinolines; Receptor, Platelet-Derived Growth Factor alpha; Regeneration; Stem Cells; Sulfides

Asthma is characterized by airflow obstruction, inflammatory cell infiltration, and the synthesis of mediators, such as T(H2) cytokines and leukotrienes, in the airways. Cysteinyl leukotriene (cysLT) receptor antagonists have recently been associated with clinical improvement of asthma and reduced airway inflammation. Whether the beneficial effects of cysLT antagonists are mediated through the modulation of cytokine expression has not been determined.. The aim of the study was to determine the presence of eosinophils and IL-5 messenger (m)RNA(+) cells within the lungs of antigen-challenged Brown Norway rats after treatment with the cysLT(1) receptor antagonist montelukast (MK).. Ovalbumin-sensitized Brown Norway rats were treated with either MK or saline before ovalbumin challenge. Pulmonary mechanics were monitored for 8 hours. Subsequently, immunocytochemistry and in situ hybridization were used to examine bronchoalveolar lavage (BAL) fluid and lung tissue for cells expressing major basic protein (eosinophils) and IL-5 mRNA, respectively. Simultaneous in situ hybridization and immunocytochemistry was used to phenotype the cells expressing mRNA encoding IL-5.. Animals treated with MK had significantly lower lung resistance and fewer eosinophils and IL-5 mRNA(+) cells within BAL fluid and lung tissue compared with that found in saline-treated animals. Colocalizaton studies revealed that the majority of IL-5 mRNA(+) cells were T cells and that the number of IL-5 mRNA(+)/CD3(+) or IL-5 mRNA(+)/major basic protein(+) cells were significantly less within BAL from animals treated with MK than from those treated with saline.. These results indicate that the cysLT(1) receptor antagonist MK can diminish the pulmonary response to antigen, tissue eosinophilia, and the number of cells expressing IL-5 mRNA, suggesting that leukotrienes may also regulate the allergic response through the modulation of inflammation and cytokine synthesis.

Topics: Acetates; Airway Resistance; Animals; Antigens; Area Under Curve; Bronchoalveolar Lavage Fluid; Cyclopropanes; Eosinophils; Gene Expression; Immunohistochemistry; Immunophenotyping; In Situ Hybridization; Interleukin-5; Leukotriene Antagonists; Lung; Myelin Basic Protein; Ovalbumin; Quinolines; Rats; Rats, Inbred BN; RNA, Messenger; Sulfides