title: Effect of combination therapy with sodium ozagrel and panax ginseng on transient cerebral ischemia model in rats.
abstract: Sodium ozagrel (SO) prevents platelet aggregation and vasoconstriction in the cerebral ischemia. It plays an important role in the prevention of brain damage induced by cerebral ischemia/reperfusion. Recently, many animal studies have suggested that the Panax ginseng (PG) has neuroprotective effects in the ischemic brain. In this study, we assessed the neuroprotective effects that come from a combination therapy of SO and PG in rat models with middle cerebral artery occlusion (MCAO). Animals with MCAO were assigned randomly to one of the following four groups: (1) control (Con) group, (2) SO group (3 mg/kg, intravenously), (3) PG group (200 mg/kg, oral feeding), and (4) SO + PG group. The rats were subjected to a neurobehavior test including adhesive removal test and rotarod test at 1, 3, 7, 10, and 15 days after MCAO. The cerebral ischemic volume was quantified by Metamorph imaging software after 2-3-5-triphenyltetrazolium (TTC) staining. The neuronal cell survival and astrocytes expansion were assessed by immunohistofluorescence staining. In the adhesive removal test, the rats of PG or SO + PG group showed significantly better performance than those of the control group (Con: 88.1 ± 24.8, PG: 43.6 ± 11, SO + PG: 11.8 ± 7, P < .05). Notably, the combination therapy group (SO + PG) showed better performance than the SO group alone (SO: 56 ± 12, SO + PG: 11.8 ± 7, P < .05). In TTC staining for infarct volume, cerebral ischemic areas were also significantly reduced in the PG group and SO + PG group (Con: 219 ± 32, PG: 117 ± 8, SO + PG: 99 ± 11, P < .05). Immunohistofluorescence staining results showed that the group which received SO + PG group therapy had neuron cells in the normal range. They also had a low number of astrocytes and apoptotic cells compared with the control or SO group in the peri-infarction area. During astrocytes staining, compared to the SO + PG group, the PG group showed only minor differences in the number of NeuN-positive cells and quantitative analysis of infarct volume. In conclusion, these studies showed that in MCAO rat models, the combination therapy with SO and PG may provide better neuroprotective effects such as higher neuronal cell survival and inhibition of astrocytes expansion than monotherapy with SO alone.
authors.affiliation: Institute of Catholic Integrative Medicine (ICIM), Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon 403-720, Republic of Korea.
authors.forename: Sang In
authors.initials: SI
authors.lastname: Park
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jang
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Han
authors.forename: Yun-Young
authors.initials: YY
authors.lastname: Sunwoo
authors.forename: Moon-Seo
authors.initials: MS
authors.lastname: Park
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Chung
authors.forename: Lee-So
authors.initials: LS
authors.lastname: Maeng
authors.forename: Ruth
authors.initials: R
authors.lastname: Im
authors.forename: Min-Wook
authors.initials: MW
authors.lastname: Kim
authors.forename: Sin-Soo
authors.initials: SS
authors.lastname: Jeun
authors.forename: Kyung-Sool
authors.initials: KS
authors.lastname: Jang
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008689:Methacrylates / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D005894:Panax; D051381:Rats
chemical_list: D034961:Antigens, Nuclear; D004365:Drugs, Chinese Herbal; D005343:Fibrinolytic Agents; D008689:Methacrylates; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C546339:Rbfox3 protein, rat; C034364:ozagrel