title: Combined neuroprotective effects of celecoxib and memantine in experimental intracerebral hemorrhage.
abstract: 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.
authors.affiliation: Stroke & Neural Stem Cell Laboratory in the Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Sinn
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Song
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: 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*
chemical_list: D039481:CD11b Antigen; D018696:Neuroprotective Agents; D011720:Pyrazoles; D013449:Sulfonamides; D053148:Caspase 3; D017364:Collagenases; D000068579:Celecoxib; D008559:Memantine