Neuronal and nonneuronal COX-2 expression confers neurotoxic and neuroprotective phenotypes in response to excitotoxin challenge.
MouseChemical/toxinTie2Cre Cox-2 flox/flox, LysMCre Cox-2 flox/flox, Cre-negative Cox-2 floxed littermates and Tie2Cre Cox-2 wild-type controlsn = 3 animals per group with 4 coronal sections each for COX-2…Intraperitoneal for drugs, intrastriatal for the excitotoxinNS-398 10 mg/kg (high) or 2 mg/kg (low); celecoxib at solut…Drugs given 1 hour before excitotoxin injection
Model: Stereotaxic intrastriatal injection of 10 microlitres of 5 micromolar (RS)-(tetrazol-5-yl)glycine at 0.8 microlitres per minute into the right striatum (anterior 0.5 mm, lateral 2.0 mm, ventral 4.0 mm to bregma) under Nembutal 100 mg/kg intraperitoneally
Deletion of COX-2 in endothelial and myeloid cells (Tie2Cre) approximately doubled lesion volume at 8 and 24 hours, indicating a protective vascular COX-2 pool, while pharmacological COX-2 inhibition with high-dose NS-398 and EP1 antagonism with SC-51089 reduced lesion volume, low-dose NS-398 or ce…
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