This Article Full Text Full Text (PDF) All Versions of this Article: 39/3/935    most recent STROKEAHA.107.501460v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Cordeau, P. Articles by Kriz, J. PubMed PubMed Citation Articles by Cordeau, P., Jr Articles by Kriz, J. Related Collections Animal models of human disease Pathology of Stroke

(Stroke. 2008;39:935.)
© 2008 American Heart Association, Inc.

Original Contributions

Live Imaging of Neuroinflammation Reveals Sex and Estrogen Effects on Astrocyte Response to Ischemic Injury

Pierre Cordeau, Jr, BSc; Mélanie Lalancette-Hébert, MS; Yuan Cheng Weng, MS Jasna Kriz, MD, PhD

From the Department of Anatomy and Physiology, Laval University, Centre de Recherche du Centre Hospitalier de l’Université Laval, Quebec, Canada.

Correspondence to Jasna Kriz, MD, PhD, Department of Anatomy and Physiology, Faculty of Medicine, Centre de Recherche du CHUL, T3-67, Université Laval, 2705 Boulevard Laurier, Québec, Canada G1V 4G2. E-mail Jasna.Kriz{at}crchul.ulaval.ca

Background and Purpose— We sought to develop a model system for live analysis of brain inflammatory response in ischemic injury.

Methods— Using a reporter mouse-expressing luciferase gene under transcriptional control of the murine glial fibrillary acidic protein (GFAP) promoter (GFAP-luc mice) and biophotonic/bioluminescent imaging as tools, we developed a model system for in vivo analysis of astrocyte activation/response in cerebral ischemia.

Results— Analysis of photon emissions from the brains of living animals revealed marked sex differences in astrocyte response to ischemic injury. The increase in GFAP signals was significantly higher in female mice in the metestrus/diestrus period compared with male transgenic mice (1.71x10⁷±0.19x10⁷ vs 0.92x10⁷±0.15x10⁷, P<0.001). Similar results were obtained by quantitative immunohistochemistry (males vs females: 13.4±0.5 vs 16.96±0.64, P<0.0001). However, astrocyte activation/GFAP signals showed cyclic, estrus-dependent variations in response to ischemic injury. Physiologically higher levels of estrogen and application of pharmacologic doses of estrogen during replacement therapy attenuated GFAP upregulation after stroke. Interestingly, contrary to a positive correlation between the intensities of GFAP signals and infarct size in male mice, no such correlation was observed in any of the experimental groups of female GFAP-luc mice.

Conclusions— Our results suggest that GFAP upregulation in ischemic injury may have different functional significance in female and male experimental animals and may not directly reflect the extent of ischemia-induced neuronal damage in female GFAP-luc mice. Using a novel live imaging approach, we demonstrated that the early-phase brain inflammatory response to ischemia may be associated with sex-specific biomarkers of brain damage.

Key Words: estrogen • glial fibrillary acidic protein • focal ischemia • gliosis • inflammation • biophotonic/bioluminescent imaging • transgenic mice