Short communicationBrain aromatase expression after experimental stroke: Topography and time course
Introduction
17β-Oestradiol administration to ovariectomised rats prior to middle cerebral artery occlusion (MCAO) has been shown in an overwhelming number of studies to significantly reduce ischaemic damage (for review see [1]). Evidence that endogenous oestrogen is neuroprotective is supported by the findings that the oestrogen receptor antagonist ICI 182,780 [2] and the aromatase inhibitor, fadrozole [3] and exacerbate ischaemic damage. In addition, aromatase expression increases in the brain in response to an injection of a neurotoxin [4].
The present study investigated whether or not brain aromatase expression was increased after an experimental stroke (MCAO) and whether this increase was in a time frame and location relevant to promoting survival of cells (i.e. in the potentially salvageable penumbral zone, which surrounds the irreversibly damaged infarct core). Stroke prone spontaneously hypertensive rats (SHRSP) were used in the present study due to their similarity of stroke to humans [5] and also since pro-oestrus (high endogenous oestrogen levels) confers a neuroprotective influence in this strain [6].
Section snippets
Methods and results
All experiments were carried out according to the British Home Office Guidelines, with the approval of the University of Glasgow Ethical Review Panel, and subject to the Animals (Scientific Procedures) Act, 1986. Ovariectomised female SHRSP (3–4 months of age; colony maintained by A.F. Dominiczak) underwent left distal MCAO by electrocoagulation to produce a predominantly cortical infarct [6]. Immunohistochemical analysis of sections (paraformaldehyde-fixed; paraffin-embedded) at the coronal
Discussion
The key findings in the present study are that brain aromatase levels are increased after stroke and the pattern and timing of this expression is commensurate with a potential role in cell survival. Increased expression was found in the penumbral/peri-infarct region where injured cells have survived the initial ischaemic insult but could later become incorporated into the irreversibly damaged infarct core if unsupported. This combined with the time course of increased aromatase expression (24 h
Acknowledgement
This work was supported by a research fellowship to H.C. from Research into Ageing (Grant No. 230).
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