Remyelination is the generation of new myelin sheaths after injury facilitated by processes of differentiating oligodendrocyte precursor cells (OPCs). Although this repair phenomenon occurs in lesions of multiple sclerosis patients, many lesions fail to completely remyelinate. A number of factors have been identified that contribute to remyelination failure, including the upregulated chondroitin sulfate proteoglycans (CSPGs) that comprise part of the astrogliotic scar. We show that in vitro, OPCs have dramatically reduced process outgrowth in the presence of CSPGs, and a medication library that includes a number of recently reported OPC differentiation drugs failed to rescue this inhibitory phenotype on CSPGs. We introduce a novel CSPG synthesis inhibitor to reduce CSPG content and find rescued process outgrowth from OPCs in vitro and accelerated remyelination following focal demyelination in mice. Preventing CSPG deposition into the lesion microenvironment may be a useful strategy to promote repair in multiple sclerosis and other neurological disorders.

No abstract

No abstract

In this study, a pH-controlled core-shell structured site-specific magnetic nanocomposite for drug delivery was reported. Superparamagnetic Fe 3 O 4 nanoparticles were selected to build its core for magnetic guiding purpose and mesoporous silica molecular sieve MCM-41 was chosen to construct its outer shell. The MCM-41 outer shell has highly ordered hexagonal tunnels therefore would offered enough cargo space for drug molecules. An organic ligand N1-(5H-cyclopenta[1,2-b:5,4-b 0 ]dipyridin-5-ylidene)benzene-1,4-diamine (denoted as Dafo-Ph-NH 2 ) was linked to the molecular sieve outer shell. There are two nitrogen atoms at the end of the ligand which are able to donate their lone pair electrons. Acidic drug molecules therefore can be bound to the ligand via weak acid-base reaction. Those drug molecules can be release in low pH solution since the H ? in the solution will compete with the ligand. The final composite was analyzed by electron microscope images, XRD, IR spectra, thermogravimetry and N 2 adsorption/desorption. Its bio-compatibility was evaluated by MTT using L929 fibroblast cell line. Our Dafo-MCM-41@Fe 3 O 4 composite shows pHcontrolled and site-specific smart release properties for aspirin in vitro.