EDT, a tetrahydroacridine derivative inhibits cerebral ischemia and protects rat cortical neurons against glutamate-induced cytotoxicity.

AIM: To study the effects of 9-(4-ethoxycarbonylyphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydroacridine (EDT) on cerebral ischemia and glutamic acid (Glu) and sodium nitroprusside (SNP)-induced neurocytotoxicity in primary cortical culture. METHODS: Focal cerebral ischemia was produced by permanent occlusion of left middle cerebral artery (MCA) in mice. The infarct tissue was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining technique. The extent of neurological deficits was evaluated. In primary cortical culture, colorimetric MTT assay was used to determine cell survival rate, and leakage of LDH and NO release assay were measured. RESULTS: In focal cerebral ischemia, pretreatment with EDT 2.5, 5, and 10 mg/kg and nimodipine 2 mg/kg for 5 d effectively improved the abnormal neurological symptoms and reduced the infarct rate. In primary cortical culture, EDT 0.01-3 micromol/L concentration-dependently attenuated NO release induced by Glu 500 micromol/L and increased the cell survival. It also remarkably reduced the LDH excessive efflux. CONCLUSION: EDT possessed protective effects against cerebral ischemia, which may be related to blocking Glu receptor and inhibiting NO formation.