PROTECTIVE EFFECT OFDL-3-N-BUTYLPHTHALIDE ON ISCHEMIC NEUROLOGICAL DAMAGE AND ABNORMAL BEHAVIOR IN RATSUBJECTED TO FOCAL ISCHEMIA

dl-3-n-Butylphthalide(NBP)was known to have improving effect on brain energy metabolism after ischemia insult.The purpose of this study is to determine if the drug has protective action against ischemic neuronal damage, In the present study , the effect of NBP on cerebral infarc-tion and neurological deficits aftermiddle cerebral artery occlusion(MCAO) in rats was investigated. Focal cerebral ischemia was preducedby permanent occl usion of the proximal portion of the right middle cerebral artery (MCA)according to the technique of Tam ura1.The infarct area was measured by 2,3,5- triphenyltetrazolium chloride(TTC)staining technique. The extent of neurologicaldeficits was evaluated by the method of Bederson2. The histological changes in neuronal change after MCAOinrats were also studied.Theresultsindicatethat theinfarctarea andthescore of ne u rol ogjcaldeficitsafterMCAOwere reduced significantly fol lowing intraperitoneal pretreatment or pre- and pot-treatment with NBP20mg·kg^-1. The treatment with NBP 10 or 20mg·kg^-1(ip), or 20,40 or 80 mg·kg^-1 (po)15min and even 2h(20 mg·kg^-1 ,ip) after MCAO also markedly reduced the infarct area and the scoreofneurologicaldeficits.However , no effect was found when NBP(20 mg·kg-1 )was injected intraperitoneally4hafter MCAO,MK- 801 ( 0. 5 mg·kg^-1,ip), a non-competitive antagonist of NMDA receptor,significantly reduced the size of infarction and the score of neurological deficits in rats subjected to MCAO, The potency of NBP in reducing the infarct area and neurological deficits was found to be quite similar to that of MK-80 1 (0.5 mg·kg^-1 ,ip).No neuroprotective effect of nimodipine(1.0 mg·kg^-1,sc)was found.Generally,the potency of NBP in protecting rats from ischemic neurological damage is equal to that of MK-80l and is more powerful than that of Nimedipine, Side effects of NBP in behavior was not found. Therefore, NBP seems to be a hopeful drug for the treatment of stroke.