Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion

Inhibitors of cell-swelling-activated anion channels, including the antiest rogenic compound tamoxifen (TAM), have been shown to attenuate the increase in excitatory amino acids (EAA) during ischemia. Since TAM enters the CNS we tested whether it provides protection from damage due to reversible midd le cerebral artery occlusion (rMCAo) in rats. TAM (5 mg/kg, i.v.) infused 2 5 min before ischemia, potently reduced the total volume of the infarct fro m 328 +/- 34 mm(3) to 41 +/- 21 mm(3), a reduction of 87%, as measured by T TC staining. It was equally effective when infused starting at 1 h after re perfusion, i.e. 3 h after initiation of rMCAo. Protection of neurons was al so found histologically. TAM had no effect on CBF as measured by hydrogen c learance. This appears to be the first report of a marked neuroprotective e ffect of TAM. Further studies are needed to determine whether its effects a re due to inhibition of EAA release and/or other potential neuroprotective sites of action. (C) 2000 Lippincott Williams & Wilkins.