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Photothrombotic Stroke Induces Persistent Ipsilateral and Contralateral Astrogliosis in Key Cognitive Control Nuclei

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Abstract

While astrocytes are recognised to play a central role in repair processes following stroke, at this stage we do not have a clear understanding of how these cells are engaged during the chronic recovery phase. Accordingly, the principal aim of this study was to undertake a quantitative multi-regional investigation of astrocytes throughout the recovery process. Specifically, we have induced experimental vascular occlusion using cold-light photothrombotic occlusion of the somatosensory/motor cortex in adult male C57B6 mice. Four weeks following occlusion we collected, processed, and immunolabelled tissue using an antibody directed at the glial fibrillary acidic protein (GFAP), an astrocyte specific cytoskeletal protein marker. We investigated GFAP changes in 13 regions in both the contra- and ipsi-lateral hemispheres from control and occluded animals. Specifically, we examined the infra-limbic (A24a), pre-limbic (A25), anterior cingulate (A32), motor (M1 and M2) cortices, the forceps minor fibre tract, as well the shell of the accumbens, thalamus, cingulate cortex (A29c), hippocampus (CA1-3) and lateral hypothalamus. Tissue from occluded animals was compared against sham treated controls. We have identified that the focal occlusion produced significant astrogliosis (p < 0.05), as defined by a marked elevation in GFAP expression, within all 13 sites assessed within the ipsilateral (lesioned) hemisphere. We further observed significant increases in GFAP expression (p < 0.05) in 9 of the 13 contralesional sites examined. This work underscores that both the ipsilateral and contralesional hemispheres, at sites distal to the infarct, are very active many weeks after the initial occlusion, a finding that potentially has significant implications for understanding and improving the regeneration of the damaged brain.

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Acknowledgments

F. R. W. acknowledges project Grant support from the Australian National Health and Medical Research Council. M. N acknowledges the support from the University of Newcastle’s Brawn Fellowship, the Hunter Medical Research Institute (HMRI) and the Sten A. Olsson Foundation for Science and Culture.

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Authors and Affiliations

  1. School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia

    Madeleine J. Patience, Ihssane Zouikr, Kim Jones & Frederick R. Walker

  2. The Centre for Translational Neuroscience and Mental Health Research, Callaghan, NSW, Australia

    Madeleine J. Patience, Ihssane Zouikr, Kim Jones & Frederick R. Walker

  3. University of Newcastle, Callaghan, NSW, Australia

    Jörgen Isgaard & Michael Nilsson

  4. Hunter Medical Research Institute, Newcastle, NSW, Australia

    Madeleine J. Patience, Ihssane Zouikr, Kim Jones, Frederick R. Walker & Michael Nilsson

  5. Department of Anatomy, The Brain Health Research Center, University of Otago, Dunedin, 9054, New Zealand

    Andrew N. Clarkson

  6. Centre for Translational Physiology, University of Otago Wellington, Dunedin, 9054, New Zealand

    Andrew N. Clarkson

  7. Department of Psychology, University of Otago, Dunedin, 9054, New Zealand

    Andrew N. Clarkson

  8. Laboratory of Experimental Endocrinology, Department of Internal Medicine, Sahlgrenska Academy at the University of Gothenburg, 413 45, Gothenburg, Sweden

    Jörgen Isgaard

  9. School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, NSW, Australia

    Sarah J. Johnson

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  1. Madeleine J. Patience
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  2. Ihssane Zouikr
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  3. Kim Jones
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  8. Michael Nilsson
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Corresponding author

Correspondence to Michael Nilsson.

Additional information

Special Issue: In honor of Michael Norenberg.

Madeleine J Patience and Ihssane Zouikr have contributed equally to this work.

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Patience, M.J., Zouikr, I., Jones, K. et al. Photothrombotic Stroke Induces Persistent Ipsilateral and Contralateral Astrogliosis in Key Cognitive Control Nuclei. Neurochem Res 40, 362–371 (2015). https://doi.org/10.1007/s11064-014-1487-8

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  • DOI: https://doi.org/10.1007/s11064-014-1487-8

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