Long-term neuroprotective effects of memantine on focal cerebral ischemia in rats
AIM: To evaluate the long-term neuroprotective effects of memantine (MEM) on transient focal cerebral ischemic injury in rats. METHODS: Seventy male Spraque-Dawley rats were radomly divided into sham( n = 6), control( n = 16), MEM 5 (n =16), MEM 10(n = 16) and MEM 20(n = 16) groups. Each group except sham group were subjected to focal cerebral ischmia induced by middle cerebral artery occlusion (MCAO) for 2 h. MEM 5,MEM 10 and MEM 20 groups were administered intraperitoneally memantine 5,10 and 20 mg/kg respectively 15 min after focal cerebral ischemia. Control group were administered intraperitoneally normal saline of the same volume as memantine groups 15 rain after focal cerebral ischemia. After 7 d period of reperfusion, the animals were examined for neurological behavior scores and then killed to measure the infarct volumes and the content of TNFα and IL-6.RESULTS: The neurological behavior scores were better in MEM 10 and MEM 20 groups than those in control group, and the neurological score was better in MEM 20 group than that in MEM 10group, but no statistical difference was found between MEM 5 group and control group. The infarct volumes in MEM 10(27.06 ±6.6) % and MEM 20 groups( 21.32 ± I0.76 ) % were significantly smaller than those in control group( 41.3 ± 6.48 ) % ( P < 0.01 ) ,and the infarct volume in MEM 20 group significantly smaller than that in MEM 10 group( P <0.01 ), but no statistical difference was found between MEM 5 ( 35.98 ± 11.07 ) % and control group. The contents of TNFα and IL-6 were significantly increased in control group compared with those in sham group( P < 0.01 ). The cantents of TNFα and IL-6 were signafieantly decreased in MEM 10 group(5.72 ±0.60), ( 135.33 ±9.80) μg/L and MEM 20 group (5.28 ± 0.66), ( 123.67 ± 8.60) μg/L compared with those in control group( P < 0. 01 ). There is no statistical differences between MEM 5 group and control group. CONCLUSION: Memantine has long-term neuroprotective effects against focal cerebral ischemic injury in a dose-deperndent manner and the neuroprotective mechanism may be related to reducing the levels of TNFα and IL-6 in brain tissues.
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维普
