Therapeutic time window of flurbiprofen axetil's neuroprotective effect in a rat model of transient focal cerebral ischemia.
BACKGROUND
The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats.


METHODS
Forty-eight male SD rats were randomly assigned into six groups (n = 8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n = 8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R.


RESULTS
The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12 - 24 hours after ischemia reperfusion.


CONCLUSIONS
COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12 - 24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.
Wang
Chen
C
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. wangchen@fmmu.edu.cn
Liu
Jun-le
JL
Sang
Han-fei
HF
Lu
Yan
Y
Dong
Hai-long
HL
Xiong
Li-ze
LZ
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005480:Flurbiprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen; C504422:flurbiprofen axetil