title: Neutralization of inhibitory molecule NG2 improves synaptic transmission, retrograde transport, and locomotor function after spinal cord injury in adult rats.
abstract: NG2 belongs to the family of chondroitin sulfate proteoglycans that are upregulated after spinal cord injury (SCI) and are major inhibitory factors restricting the growth of fibers after SCI. Neutralization of NG2's inhibitory effect on axon growth by anti-NG2 monoclonal antibodies (NG2-Ab) has been reported. In addition, recent studies show that exogenous NG2 induces a block of axonal conduction. In this study, we demonstrate that acute intraspinal injections of NG2-Ab prevented an acute block of conduction by NG2. Chronic intrathecal infusion of NG2-Ab improved the following deficits induced by chronic midthoracic lateral hemisection (HX) injury: (1) synaptic transmission to lumbar motoneurons, (2) retrograde transport of fluororuby anatomical tracer from L5 to L1, and (3) locomotor function assessed by automated CatWalk gait analysis. We collected data in an attempt to understand the cellular and molecular mechanisms underlying the NG2-Ab-induced improvement of synaptic transmission in HX-injured spinal cord. These data showed the following: (1) that chronic NG2-Ab infusion improved conduction and axonal excitability in chronically HX-injured rats, (2) that antibody treatment increased the density of serotonergic axons with ventral regions of spinal segments L1-L5, (3) and that NG2-positive processes contact nodes of Ranvier within the nodal gap at the location of nodal Na(+) channels, which are known to be critical for propagation of action potentials along axons. Together, these results demonstrate that treatment with NG2-Ab partially improves both synaptic and anatomical plasticity in damaged spinal cord and promotes functional recovery after HX SCI. Neutralizing antibodies against NG2 may be an excellent way to promote axonal conduction after SCI.
authors: Northport Veterans Affairs Medical Center, Northport, New York 11768, USA.
authors: Hayk A
authors: HA
authors: Petrosyan
authors: Arsen S
authors: AS
authors: Hunanyan
authors: Valentina
authors: V
authors: Alessi
authors: Lisa
authors: L
authors: Schnell
authors: Joel
authors: J
authors: Levine
authors: Victor L
authors: VL
authors: Arvanian
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000941:Antigens / Q000276:immunology* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007839:Functional Laterality; D005684:Gait / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011509:Proteoglycans / Q000276:immunology* / Q000494:pharmacology; D011901:Ranvier's Nodes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D015816:Cell Adhesion Molecules, Neuronal; D003911:Dextrans; D011509:Proteoglycans; D012235:Rhodamines; D012701:Serotonin; D015222:Sodium Channels; D000099216:Chondroitin Sulfate Proteoglycan 4; C105177:Cntnap1 protein, rat; C067661:Fluoro-Ruby