Tamoxifen treatment for intracerebral hemorrhage

Abstract

Tamoxifen is a selective estrogen receptor modulator. In this study we investigated whether or not tamoxifen reduces intracerebral hemorrhage (ICH)-induced brain injury in rats. In all experiments, adult male Sprague-Dawley rats received an injection of 100 μL autologous whole blood into the right basal ganglia. In the first set of experiments, rats were treated with tamoxifen (2.5 mg/kg or 5 mg/kg, i.p.) or vehicle 2 and 24 h after ICH and were killed at day 3 for brain edema measurement. In the second set of experiments, rats were treated with tamoxifen (5 mg/kg) or vehicle and magnetic resonance imaging (MRI), and behavior tests were performed at days 1, 7, 14 and 28. Rats were killed at day 28 for brain histology. We found that tamoxifen at 5 but not at 2.5 mg/kg reduced perihematomal brain edema at day 3 (p < 0.05). Brain histology showed that tamoxifen reduced caudate atrophy at day 28 (p < 0.01). Tamoxifen also improved functional outcome (p < 0.05). MRI demonstrated a tendency to smaller T2*lesions in tamoxifen-treated rats. However, two out of five rats treated with tamoxifen developed hydrocephalus. These results suggest that tamoxifen has neuroprotective effects in ICH, but the cause of hydrocephalus development following tamoxifen treatment needs to be examined further. © 2011 Springer-Verlag/Wien.