Cognitive recovery in the aged rat after stroke and anti-Nogo-A immunotherapy.
We have previously shown that immunotherapy directed against the protein Nogo-A leads to recovery on a skilled forelimb reaching task in rats after sensorimotor cortex stroke, which correlated with axonal and dendritic plasticity. Here we investigated anti-Nogo-A immunotherapy as an intervention to improve performance on a spatial memory task in aged rats after stroke, and whether cognitive recovery was correlated with structural plasticity. Aged rats underwent a unilateral distal permanent middle cerebral artery occlusion and one week later were treated with an anti-Nogo-A or control antibody. Nine weeks post-stroke, treated rats and normal aged rats were tested on the Morris water maze task. Following testing rats were sacrificed and brains processed for the Golgi-Cox method. Hippocampal CA3 and CA1 pyramidal and dentate gyrus granule cells were examined for dendritic length and number of branch segments, and CA3 and CA1 pyramidal cells were examined for spine density and morphology. Anti-Nogo-A immunotherapy given one week following stroke in aged rats improved performance on the reference memory portion of the Morris water maze task. However, this improved performance was not correlated with structural changes in the hippocampal neurons examined. Our finding of improved performance on the Morris water maze in aged rats after stroke and treatment with anti-Nogo-A immunotherapy demonstrates the promising therapeutic potential for anti-Nogo-A immunotherapy to treat cognitive deficits after stroke. The identification of sites of axonal and dendritic plasticity in the aged brain after stroke and treatment with anti-Nogo-A immunotherapy is still under investigation.
Gillani
Rebecca L
RL
Neuroscience Program, Loyola University Chicago, Maywood, IL 60153, USA. resmith@lumc.edu
Tsai
Shih-Yen
SY
Wallace
Douglas G
DG
O'Brien
Timothy E
TE
Arhebamen
Ebinehita
E
Tole
Mateo
M
Schwab
Martin E
ME
Kartje
Gwendolyn L
GL
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D003072:Cognition Disorders / Q000209:etiology / Q000276:immunology / Q000628:therapy; D003712:Dendrites / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007167:Immunotherapy / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000473:pathology; D007270:Injections, Intra-Articular / Q000379:methods; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000502:physiology; D009185:Myelin Proteins / Q000276:immunology*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D000070798:Nogo Proteins; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D016622:Silver Staining / Q000379:methods
D000906:Antibodies; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat