Chronic inhibition of cyclooxygenase-2 induces dendritic hypertrophy and limited functional improvement following motor cortex stroke.
The cyclooxygenase-2 (COX-2) enzyme is part of the inflammatory pathway and is induced within the brain by a variety of pathological events, including ischemia. Pharmacological agents that inhibit COX-2 have been found to be neuroprotective in a number of injury models, and long-term administration of these drugs has been shown to induce plastic changes in the brain. In the current experiment, we investigated the effectiveness of stimulating cortical plasticity following stroke injury through the administration of the COX-2 inhibitor drug NS398. Furthermore, we determined whether the induced plastic changes improved functional outcome following motor cortex stroke. Chronic drug administration was found to induce dendritic hypertrophy in cells in the parietal cortex, and this anatomical change was associated with the animals making significantly more reach attempts, as well as successful reaches during a skilled reaching task. Additional motor tests however revealed that the treatment did not affect the level of motor recovery, as the animals showed chronic impairments in the Schallert cylinder, and the forepaw inhibition tasks. Short-term administration of the drug, immediately following the stroke did not induce any dendritic changes, nor was it found to improve behavioral performance on any of the motor tasks. Based on these results we conclude that the plastic changes that are induced by long-term COX-2 inhibitor administration provide some benefit to functional outcome following ischemic cortical injury.
Silasi
G
G
Department of Psychology and Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada. silasi@ualberta.ca
Kolb
B
B
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D003712:Dendrites / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D005552:Forelimb / Q000294:innervation / Q000503:physiopathology; D006984:Hypertrophy / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D009578:Nitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use; D010291:Paresis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2