[Protective effect of dl-3-n-butylphthalide on ischemic neurological damage and abnormal behavior in rats subjected 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 infarction and neurological deficits after middle cerebral artery occlusion (MCAO) in rats was investigated. Focal cerebral ischemia was produced by permanent occlusion of the proximal portion of the right middle cerebral artery (MCA) according to the technique of Tamura. The infarct area was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining technique. The extent of neurological deficits was evaluated by the method of Bederson. The histological changes in neuronal change after MCAO in rats were also studied. The results indicate that the infarct area and the score of neurological deficits after MCAO were reduced significantly following intraperitoneal pretreatment or pre- and post-treatment with NBP 20 mg . kg-1. The treatment with NBP 10 or 20 mg . kg-1(i.p.), or 20,40 or 80 mg . kg-1 (po) 15 min and even 2 h (20 mg . kg-1, i.p.) after MCAO also markedly reduced the infarct area and the score of neurological deficits. However, no effect was found when NBP (20 mg . kg-1) was injected intraperitoneally 4 h after MCAO. MK-801 (0.5 mg . kg-1, i.p.), 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-801 (0.5 mg . kg-1, i.p.). 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-801 and is more powerful than that of Nimodipine. Side effects of NBP in behavior was not found. Therefore, NBP seems to be a hopeful drug for the treatment of stroke.
Liu
X G
XG
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Feng
Y P
YP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001572:Benzofurans / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009553:Nimodipine / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000627:therapeutic use
D001572:Benzofurans; D018696:Neuroprotective Agents; D014665:Vasodilator Agents; D009553:Nimodipine; D016291:Dizocilpine Maleate; C027125:3-n-butylphthalide