title: Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity.
abstract: After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo-NogoReceptor (NgR) pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Mutant mice lacking NgR or Nogo-AB recover complex motor function after stroke more completely than do control animals. After a stroke, greater numbers of axons emanating from the undamaged cortex cross the midline to innervate the contralateral red nucleus and the ipsilateral cervical spinal cord; this axonal plasticity is enhanced in ngr -/- or nogo-ab -/- mice. In rats with middle cerebral artery occlusion, both the recovery of motor skills and corticofugal axonal plasticity are promoted by intracerebroventricular administration of a function-blocking NgR fragment. Behavioral improvement occurs when therapy is initiated 1 week after arterial occlusion. Thus, delayed pharmacological blockade of the NgR promotes subacute stroke recovery by facilitating axonal plasticity.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Jung-Kil
authors.initials: JK
authors.lastname: Lee
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Sivula
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects / Q000235:genetics*; D020521:Stroke / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; C495858:NgR(310) Ecto-Fc protein; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C419790:Rtn4r protein, mouse; C486581:Rtn4r protein, rat