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


CONCLUSIONS
EDT possessed protective effects against cerebral ischemia, which may be related to blocking Glu receptor and inhibiting NO formation.
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. sheng_rui@163.com
Rui
R
Sheng
Guo-Qing
GQ
Liu
D000166:Acridines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
C477692:9-(4-ethoxycarbonylyphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydroacridine; D000166:Acridines; D018696:Neuroprotective Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase