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A mouse model of cerebral oligemia: relation to brain histopathology, cerebral blood flow, and energy state

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Abstract

An animal model involving stepwise occlusion of the common carotid arteries (sCCAO) in DBA/2 mice is presented in which the right and left carotid arteries were permanently ligated within a time interval of four weeks. Thereafter, cerebral functional and structural parameters were determined at acute (15 min) and subchronic (1 day; 3, 7, and 14 days) time points after sCCAO. Quantitative changes in regional cerebral blood flow (rCBF) as determined by the [14C]iodoantipyrine method, energy state (ATP, phosphocreatine, ADP, AMP, adenosine) as shown by HPLC, brain histopathology, and neuronal densities were measured in both hemispheres. Acute sCCAO was accompanied by a drastic reduction in cerebral energy-rich phosphate concentrations, ATP and phosphocreatine, and in rCBF of more than 50%. In contrast, cortical adenosine increased around five-fold. Subchronic sCCAO, however, was associated with normalization in brain energy metabolites and near-complete restoration of rCBF, except in the caudate nucleus (−40%). No marked signs of necrotic or apoptotic cell destruction were detected. Thus, during the subchronic period, compensatory mechanisms are induced to counteract the drastic changes seen after acute vessel occlusion. In conclusion, this sCCAO mouse model may be useful for long-lasting investigations of stepwise deterioration contributing to chronic cerebrovascular disorders.

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Acknowledgements

The authors would like to thank Roland Galmbacher, Stephan Hennes, Sigrid Kirchmeier, and Sebastian Hennig for their excellent technical assistance. This study was supported in part by the Medical Faculty of the University of Heidelberg (Forschungsschwerpunkt Geriatrie).

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Author notes

  1. Clemens Sommer

    Present address: Laboratory of Neuropathology, University of Ulm, Ulm, Germany

Authors and Affiliations

  1. Clinic of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Konstanze Plaschke, Eike Martin, Markus A. Weigand & Hubert J. Bardenheuer

  2. Institute of Neuropathology, University of Heidelberg, Heidelberg, Germany

    Clemens Sommer, Dejana Matejic & Marika Kiessling

  3. Institute of Physiology, University of Heidelberg, Heidelberg, Germany

    Helmut Schroeck

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  1. Konstanze Plaschke
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  8. Hubert J. Bardenheuer
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Correspondence to Konstanze Plaschke.

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Plaschke, K., Sommer, C., Schroeck, H. et al. A mouse model of cerebral oligemia: relation to brain histopathology, cerebral blood flow, and energy state. Exp Brain Res 162, 324–331 (2005). https://doi.org/10.1007/s00221-004-2177-6

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  • DOI: https://doi.org/10.1007/s00221-004-2177-6

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