title: Potential Benefit of the Charge-Stabilized Nanostructure Saline RNS60 for Myelin Maintenance and Repair.
abstract: Myelin injury in multiple sclerosis (MS) has been attributed both to "outside-in" primary immune mediated and "inside-out" metabolic stress of oligodendrocyte (OL) related mechanisms. Subsequent remyelination is dependent on recruitment and differentiation of oligodendrocyte progenitor cells (OPCs). RNS60 is a physically-modified saline containing charge-stabilized nanobubbles generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. Administration of RNS60 has been shown to reduce the severity of EAE by dampening the immune response and myelin loss. Additionally, RNS60 has been demonstrated to enhance mitochondrial ATP synthesis in neurons. Here, we used post-natal rat derived OLs and OPCs to assess the impact of RNS60 on the response of OLs to metabolic stress in vitro (glucose-nutrient deprivation, referred to as 'NG') and on OPC differentiation capacity. Under the NG condition, our findings indicate that RNS60 decreases caspases 3/7 activation. Respirometric analyses revealed that RNS60 increased spare glycolytic capacity (SGC) under normal culture conditions. However, RNS60 enhanced OL spare respiratory capacity (SRC) when a metabolic stress was present. Furthermore, we show that RNS60 promotes OPC differentiation under physiological conditions. Our findings provide evidence for the potential therapeutic efficacy of RNS60 through the promotion of OL survival and OPC differentiation.
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Vijayaraghava T S
authors.initials: VT
authors.lastname: Rao
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Damla
authors.initials: D
authors.lastname: Khan
authors.affiliation: Department of Physiology, McGill University, Montréal, Quebec, Canada.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Jones
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Diane S
authors.initials: DS
authors.lastname: Nakamura
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kennedy
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Cui
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Malena B
authors.initials: MB
authors.lastname: Rone
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Luke M
authors.initials: LM
authors.lastname: Healy
authors.affiliation: Revalesio Corporation, Tacoma, Washington, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Watson
authors.affiliation: Revalesio Corporation, Tacoma, Washington, USA.
authors.forename: Supurna
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology; D006019:Glycolysis / Q000187:drug effects; D009103:Multiple Sclerosis / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology*; D058953:Neural Stem Cells / Q000166:cytology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074586:Remyelination / Q000502:physiology*; D012965:Sodium Chloride / Q000737:chemistry / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; C000627108:RNS60; D012965:Sodium Chloride; D010100:Oxygen