title: An ex-vivo multiple sclerosis model of inflammatory demyelination using hyperbranched polymer.
abstract: Multiple sclerosis (MS) is characterized by the presence of inflammatory demyelinating foci throughout the brain and spinal cord, accompanied by axonal and neuronal damage. Although inflammatory processes are thought to underlie the pathological changes, the individual mediators of this damage are unclear. In order to study the role of pro-inflammatory cytokines in demyelination in the central nervous system, we have utilized a hyperbranched poly(2-dimethyl-aminoethylmethacrylate) based non-viral gene transfection system to establish an inflammatory demyelinating model of MS in an ex-vivo environment. The synthesized non-viral gene transfection system was optimized for efficient transfection with minimal cytotoxicity. Organotypic brain slices were then successfully transfected with the TNF or IFNγ genes. TNF and IFNγ expression and release in cerebellar slices via non-viral gene delivery approach resulted in inflammation mediated myelin loss, thus making it a promising ex-vivo approach for studying the underlying mechanisms of demyelination in myelin-related diseases such as MS.
authors: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors: Asha
authors: A
authors: Mathew
authors: Janelle M P
authors: JM
authors: Pakan
authors: Estelle C
authors: EC
authors: Collin
authors: Wenxin
authors: W
authors: Wang
authors: Kieran W
authors: KW
authors: McDermott
authors: Una
authors: U
authors: Fitzgerald
authors: Richard
authors: R
authors: Reynolds
authors: Abhay S
authors: AS
authors: Pandit
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003711:Demyelinating Diseases / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism; D008689:Methacrylates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008689:Methacrylates; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; C051774:neurofilament protein H; D007371:Interferon-gamma; C049840:2-(dimethylamino)ethyl methacrylate