Anti-Nogo-A antibody infusion 24 hours after experimental stroke improved behavioral outcome and corticospinal plasticity in normotensive and spontaneously hypertensive rats

J Cereb Blood Flow Metab. 2003 Feb;23(2):154-65. doi: 10.1097/01.WCB.0000040400.30600.AF.


Nogo-A is a myelin-associated neurite outgrowth inhibitory protein limiting recovery and plasticity after central nervous system injury. In this study, a purified monoclonal anti-Nogo-A antibody (7B12) was evaluated in two rat stroke models with a time-to-treatment of 24 hours after injury. After photothrombotic cortical injury (PCI) and intraventricular infusion of a control mouse immunoglobulin G for 2 weeks, long-term contralateral forepaw function was reduced to about 55% of prelesion performance until the latest time point investigated (9 weeks). Forepaw function was significantly better in the 7B12-treated group 6 to 9 weeks after PCI, and reached about 70% of prelesion levels. Cortical infarcts were also produced in spontaneously hypertensive rats (SHR) by permanent middle cerebral artery occlusion (MCAO). In the control group, forepaw function remained between 40% and 50% of prelesion levels 4 to 12 weeks after MCAO. In contrast, 7B12-treated groups showed significant improvement between 4 and 7 weeks after MCAO from around 40% of prelesion levels at week 4 to about 60% to 70% at 7 to 12 weeks after MCAO. Treatment in both models was efficacious without influencing infarct volume or brain atrophy. Neuroanatomically in the spinal cord, a significant increase of midline crossing corticospinal fibers originating in the unlesioned sensorimotor cortex was found in 7B12-treated groups, reaching 2.3 +/- 1.5% after PCI (control group: 1.1 +/- 0.5%) and 4.5 +/- 2.2% after MCAO in SHR rats (control group: 1.8 +/- 0.8%). Behavioral outcome and the presence of midline crossing fibers in the cervical spinal cord correlated significantly, suggesting a possible contribution of the crossing fibers for forepaw function after PCI and MCAO. The results suggest that specific anti-Nogo-A antibodies bear potential as a new rehabilitative treatment approach for ischemic stroke with a prolonged time-to-treatment window.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / pharmacokinetics
  • Arterial Occlusive Diseases / complications
  • Behavior, Animal / drug effects*
  • Brain / metabolism
  • Cerebral Arteries
  • Cerebral Infarction / etiology
  • Cerebral Infarction / pathology
  • Cerebral Infarction / psychology
  • Drug Administration Schedule
  • Hypertension / complications*
  • Injections, Intraventricular
  • Male
  • Myelin Proteins / immunology*
  • Neuronal Plasticity / drug effects
  • Nogo Proteins
  • Pyramidal Tracts / pathology
  • Pyramidal Tracts / physiopathology
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred SHR
  • Stroke / etiology
  • Stroke / physiopathology*
  • Stroke / psychology*
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Myelin Proteins
  • Nogo Proteins
  • Rtn4 protein, mouse
  • Rtn4 protein, rat