Combined neuroprotective effects of celecoxib and memantine in experimental intracerebral hemorrhage.
Memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, inhibits hematoma expansion and celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduces perihematomal inflammation in intracerebral hemorrhage. We examined whether the combination treatment has additive effects in experimental intracerebral hemorrhage (ICH). ICH was induced using stereotaxic infusion of collagenase into brains of adult rats. After the induction of ICH, rats were treated with intraperitoneal injection of memantine (20 mg/kg), celecoxib (20 mg/kg) or both agents. Only vehicles were administrated in rats of the control group. Results showed that the combination treatment of memantine and celecoxib reduced both hematoma volume and brain edema. Combination treatment also induced the better functional recovery with further attenuation of cerebral inflammation and apoptosis compared to the control group. When compared to the single agent groups, the combination treatment showed better effects in neuroprotection and anti-inflammation. These results suggest the feasible combined application of memantine and celecoxib in ICH treatment.
Sinn
Dong-In
DI
Stroke & Neural Stem Cell Laboratory in the Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Lee
Soon-Tae
ST
Chu
Kon
K
Jung
Keun-Hwa
KH
Song
Eun-Cheol
EC
Kim
Jeong-Min
JM
Park
Dong-Kyu
DK
Kim
Manho
M
Roh
Jae-Kyu
JK
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D000068579:Celecoxib; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000188:drug therapy*; D017364:Collagenases; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007839:Functional Laterality; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
D039481:CD11b Antigen; D018696:Neuroprotective Agents; D011720:Pyrazoles; D013449:Sulfonamides; D053148:Caspase 3; D017364:Collagenases; D000068579:Celecoxib; D008559:Memantine