Original Article

Journal of Cerebral Blood Flow & Metabolism (2005) 25, 247–256. doi:10.1038/sj.jcbfm.9600026

17bold italic beta-Estradiol pretreatment reduces bleeding and brain injury after intracerebral hemorrhagic stroke in male rats

Research support provided by the Canadian Stroke Network. F Colbourne is supported by an Alberta Heritage Foundation for Medical Research Medical Scholar award.

Angela Auriat1,*, Wayne C Plahta2,*, Steven C McGie2, Reginia Yan1 and Frederick Colbourne1,2

  1. 1Department of Psychology, University of Alberta, Edmonton, AB, Canada
  2. 2Centre for Neuroscience, University of Alberta, Edmonton, AB, Canada

Correspondence: Dr F Colbourne, Department of Psychology, Faculty of Science, P217 Biological Sciences Building, University of Alberta, Edmonton, AB, Canada, T6G 2E9. E-mail: fcolbour@ualberta.ca

*These authors contributed equally to this project.

Received 19 February 2004; Revised 24 May 2004; Accepted 1 October 2004.

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Abstract

17beta-estradiol reduces cell death after global and focal ischemia and subarachnoid hemorrhage in rodents. Presently, we tested whether estrogen improves outcome after intracerebral hemorrhage (ICH) in male rats. Rats were implanted subcutaneously with 0.05, 0.25, or 0.50 mg pellets of estrogen (21-day release) or subjected to a sham procedure. Two weeks after implantation, they were given a striatal ICH via an infusion of collagenase. The three estrogen groups had significantly smaller lesions at a 7-day survival. Some rats had core temperature measured with an implanted telemetry probe, which also measured whole-body movements. Estrogen did not affect temperature nor activity levels after ICH. A second study with 0.25 mg pellets, administered once or twice, showed persistent histologic protection (30 days) and some functional benefit (e.g., elevated beam). A spectrophotometric hemoglobin assay showed that the 0.25 mg dose significantly reduced hemorrhagic blood volume at 12 hours after ICH. Regardless, estrogen did not lessen cerebral edema at 2 days after ICH and functional benefits were not consistently found on all tests (e.g., cylinder task). In summary, estrogen pretreatment reduces injury after ICH, in part by reducing bleeding. Estrogen may thus lessen injury and improve outcome after ICH in humans.

Keywords:

activity, estrogen, intracerebral hemorrhage, temperature and neuroprotection

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