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Brain aromatase expression after experimental stroke: Topography and time course

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Abstract

Brain aromatase has been shown to be increased in expression after neurotoxic damage and to exert neuroprotection via generation of local oestrogens. The present study investigates the topography and time course of brain aromatase expression after experimental stroke (middle cerebral artery occlusion (MCAO)). Ovariectomised stroke prone spontaneously hypertensive rats underwent distal MCAO by electrocoagulation. Immunohistochemistry revealed increased brain aromatase expression at 24 h and 8 days in the cortical penumbra/peri-infarct zones with no increase evident at 2 h or 30 days post-MCAO. Double label studies indicate that some of the increased aromatase expression is associated with astrocytic processes. Thus, this is the first evidence that aromatase protein is increased after MCAO and the location (peri-infarct), time course (within 24 h) and cellular localisation (astrocytic) indicate the potential for aromatase to promote the survival of cells in the penumbra after experimental stroke by local synthesis of oestrogens.

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).

References (13)

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    Citation Excerpt :

    Indeed, the key site of aromatization in this neuroprotective effect may be the area around the lesion itself. In spontaneously hypertensive rats, MCAO increases the expression of aromatase in astrocytic processes in the penumbra of the neural infarct (Carswell et al., 2005). This upregulation is detectable at 24 h and 8 days following treatment but is not 2 h or 30 days after MCAO.

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