Acute treatment with tamoxifen reduces ischemic damage... : NeuroReport (original) (raw)

NEUROPHARMACOLOGY

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

Kimelberg, Harold K.1,2,3; Feustel, Paul J.1,2; Jin, Yiqiang2; Paquette, Justin1; Boulos, Alan1; Keller, Richard W. Jr.2; Tranmer, Bruce I.1

1Division of Neurosurgery, A-60, Department of Surgery, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA

2Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA

3Corresponding Author and Address: Harold K. Kimelberg, Division of Neurosurgery, A-60, Department of Surgery, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA

Acknowledgements: We thank Dr A. Mongin for numerous helpful discussions. This work was supported by NS 35,205 to H.K.K.

Received 3 May 2000; accepted 7 June 2000

Abstract

Inhibitors of cell-swelling-activated anion channels, including the antiestrogenic 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 middle cerebral artery occlusion (rMCAo) in rats. TAM (5 mg/kg, i.v.) infused 25 min before ischemia, potently reduced the total volume of the infarct from 328±34 mm3 to 41±21 mm3, a reduction of 87%, as measured by TTC staining. It was equally effective when infused starting at 1 h after reperfusion, i.e. 3 h after initiation of rMCAo. Protection of neurons was also found histologically. TAM had no effect on CBF as measured by hydrogen clearance. This appears to be the first report of a marked neuroprotective effect of TAM. Further studies are needed to determine whether its effects are due to inhibition of EAA release and/or other potential neuroprotective sites of action.