Histological and Elemental Changes in Ischemic Stroke
Stroke is a leading cause of serious long-term disability in adults and a leading cause of death in developed nations. Following an ischemic stroke the metabolic profile of the affected tissue is significantly altered, with the infarct representing the most severely affected tissue, and the surrounding penumbra, or peri-infarct zone (PIZ), containing a gradient of metabolic states progressing from severely impacted toward an otherwise healthy profile. The penumbra contains potentially salvageable tissue and is the focus in many stroke treatments. In this chapter, we employ the photothrombotic stroke model (a widely used animal model for studying focal ischemia) to study the histopathological and bioelemental changes that occur post-stroke. Synchrotron-based X-ray fluorescence imaging allows simultaneous measurement of multiple elements in situ within biological tissues, as their naturally-occurring concentrations. Images of elemental distributions are compared to conventional histopathological changes in the infarct and penumbra. Understanding the bioelemental changes associated with the post-stroke brain provides opportunities to expand our understanding of the underlying cellular and tissue changes associated with ischemic stroke and can ultimately be used to guide development of future treatment methods targeting the penumbra.
KeywordsIschemic stroke Penumbra Photothrombotic stroke Excitotoxicity X-ray fluorescence imaging Elemental mapping
AK was a recipient of the College of Medicine Dean’s summer research award. MEBK is the Saskatchewan Clinical Stroke Research Chair and is supported by grants from the Canadian Institutes of Health research (CIHR), the Saskatchewan Health Research Foundation, the Heart and Stroke Foundation, Saskatchewan, and the University of Saskatchewan, College of Medicine. Research described in this chapter was performed in part at the Canadian Light Source, which is supported by the Natural Sciences and Engineering Research Council of Canada, the National Research Council Canada, CIHR, and Province of Saskatchewan, Western Economic Diversification Canada, and the University of Saskatchewan. In addition, the Stanford Synchrotron Radiation Lightsource (SSRL), SLAC National Accelerator Laboratory, was used for this research and is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.
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