Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats.
Spinal cord trauma leads to loss of motor, sensory and autonomic functions below the lesion. Recovery is very restricted, due in part to neurite growth inhibitory myelin proteins, in particular Nogo-A. Two neutralizing antibodies against Nogo-A were used to study recovery and axonal regeneration after spinal cord lesions. Three months old Lewis rats were tested in sensory-motor tasks (open field locomotion, crossing of ladder rungs and narrow beams, the CatWalk(R) runway, reactions to heat and von Frey hairs). A T-shaped lesion was made at T8, and an intrathecal catheter delivered highly purified anti-Nogo-A monoclonal IgGs or unspecific IgGs for 2 weeks. A better outcome in motor behavior was obtained as early as two weeks after lesion in the animals receiving the Nogo-A antibodies. Withdrawal responses to heat and mechanical stimuli were not different between the groups. Histology showed enhanced regeneration of corticospinal axons in the anti-Nogo-A antibody groups. fMRI revealed significant cortical responses to stimulation of the hindpaw exclusively in anti-Nogo-A animals. These results demonstrate that neutralization of the neurite growth inhibitor Nogo-A by intrathecal antibodies leads to enhanced regeneration and reorganization of the injured CNS, resulting in improved recovery of compromised functions in the absence of dysfunctions.
Liebscher
Thomas
T
University and ETH Zurich, Brain Research Institute, Zurich, Switzerland.
Schnell
Lisa
L
Schnell
Dina
D
Scholl
Jeannette
J
Schneider
Regula
R
Gullo
Mirjam
M
Fouad
Karim
K
Mir
Anis
A
Rausch
Martin
M
Kindler
Diana
D
Hamers
Frank P T
FP
Schwab
Martin E
ME
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D009185:Myelin Proteins / Q000276:immunology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D000070798:Nogo Proteins; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013550:Swimming; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology
D007074:Immunoglobulin G; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat