carbocyanines and Multiple-Sclerosis

Previous data showed that myelin-reactive autoantibodies found in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis recognize and hydrolyze various fragments of myelin basic protein (MBP). Moreover, antibody-mediated cleavage of the encephalithogenic fragment MBP

Topics: Adult; Aged; Autoantibodies; Biomarkers; Carbocyanines; Diagnosis, Differential; Energy Transfer; Female; Fluorescent Dyes; Humans; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Young Adult

Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.

Topics: Animals; Carbocyanines; Drug Carriers; Encephalomyelitis, Autoimmune, Experimental; Female; Fibrin; Fluorescent Dyes; Hydrophobic and Hydrophilic Interactions; Lactones; Laminin; Membrane Glycoproteins; Multiple Sclerosis; Nanoparticles; Oligopeptides; Polyethylene Glycols; Rats; Rats, Inbred F344; Spinal Cord; Up-Regulation

Multiple sclerosis is an inflammatory disease of the central nervous system characterized by inflammation, demyelination, axonal degeneration and accumulation of neurological disability. Previously, we demonstrated that stem cells constitute a possible endogenous source for remyelination. We now addressed the question of whether neurogenesis can occur in neuroinflammatory lesions. We demonstrated that, in experimental autoimmune encephalomyelitis, induced in rats 1,1'-dioctadecyl-6,6'-di(4sulphopentyl)-3,3,3',3'tetramethylindocarbocyanin(DiI)-labelled ependymal cells not only proliferated but descendants migrated to the area of neuroinflammation and differentiated into cells expressing the neuronal markers beta-III-tubulin and NeuN. Furthermore, these cells were immunoreactive for bromodeoxyuridine and PCNA, markers for cells undergoing cell proliferation. Using the whole-cell patch-clamp technique on freshly isolated 1, DiI-labelled cells from spinal cord lesions we demonstrated the ability of these cells to fire overshooting action potentials similar to those of immature neurones. We thus provide the first evidence for the initiation of neurogenesis in neuroinflammatory lesions in the adult spinal cord.

Topics: Animals; Bromodeoxyuridine; Carbocyanines; Cell Differentiation; Cell Enlargement; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Radiation; Female; Fluorescent Antibody Technique; In Vitro Techniques; Membrane Potentials; Microscopy, Confocal; Multiple Sclerosis; Neurons; Patch-Clamp Techniques; Phosphopyruvate Hydratase; Proliferating Cell Nuclear Antigen; Rats; Spinal Cord

In the brains of 7 patients with multiple sclerosis, mast cells were observed within the demyelinated plaques, in the border zone of the plaques as well as in seemingly normal white matter. The cells were mostly located in close connection with small vessels. The routine staining with toluidine blue for the demonstration of mast cells is not adequate as compared with staining of similar sections in pinacyanol erythrosine. Mast cells may be a hitherto underestimated contributor to the demyelinating process of multiple sclerosis.

Topics: Brain; Carbocyanines; Erythrosine; Fluoresceins; Histological Techniques; Humans; Mast Cells; Microscopy, Electron; Multiple Sclerosis; Quinolines; Staining and Labeling