Post-treatment, but not pre-treatment, with the selective cyclooxygenase-2 inhibitor celecoxib markedly enhances functional recovery from kainic acid-induced neurodegeneration.
We have investigated the role of inflammation in the excitotoxicity induced by overstimulation of glutamate receptors using kainic acid, an important tool for studying functions related to excitatory amino acid transmission and for producing neuronal death, especially in areas CA1 and CA3 of the hippocampus. We hypothesised that by inhibiting one of the major components of the neuroinflammation response, after kainic acid injection, that there would be less inflammation and therefore a reduction in cell loss, an enhancement of cognitive function (using spatial learning and object exploration tasks) or both. We examined brain-derived neurotrophic factor levels, expecting that there would be a correlation between its level and subsequent recovery. Our results confirmed our hypothesis: the kainic acid injected-rats treated with celecoxib (after kainic injection) performed better in the spatial and non-spatial tasks than the kainic acid-treated group. However, there was not any improvement if celecoxib was given before kainic acid treatment, underlining also the importance of the production of prostaglandin at the beginning of inflammation.
Gobbo
O L
OL
Department of Psychology and Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
O'Mara
S M
SM
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D000068579:Celecoxib; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004924:Escape Reaction / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000517:prevention & control*; D009474:Neurons; D011597:Psychomotor Performance / Q000187:drug effects; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D007608:Kainic Acid