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  • Redistribution and Abundance of Aquaporin-4 in White and Grey Matter after Focal Cerebral Ischemia

    Final Number:

    Jesse A Stokum MS; David B Kurland BA; Volodymyr Gerzanich MD, PhD; J. Marc Simard MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2015 Annual Meeting

    Introduction: Aquaporin-4 (Aqp4) is a passive transmembrane water channel that in the CNS is expressed exclusively by astrocytes, and that has been linked to cerebral edema formation after cerebral ischemia. Following ischemia, grey matter exhibits alterations in Aqp4 protein abundance and plasmalemmal localization that likely impact edema formation. However, it is unknown if Aqp4 expression or localization differs between white and grey matter.

    Methods: We used immunoblot analysis and immunohistochemistry to examine Aqp4 protein abundance and subcellular Aqp4 localization in the cortex and lateral corpus callosum of rats subjected to a 2 hour middle cerebral artery occlusion with 2, 10, 24 or 48 hours of reperfusion. We also used immunohistochemistry to examine Aqp4 subcellular localization in the cortex and subcortical white matter of postmortem brain tissue from patients with focal ischemic stroke or control patients.

    Results: In rat ischemic cortical tissue, Aqp4 expression at the perivascular endfoot was decreased with no Aqp4 redistribution to the greater plasmalemma. In contrast, in rat ischemic lateral corpus callosum, Aqp4 expression was increased at the perivascular endfoot and at the plasmalemma over the soma and major processes. Analysis of postmortem brain tissue from stroke patients showed similar differences in Aqp4 subcellular localization between white and grey matter of ischemic tissues versus control tissues. Ischemic grey matter exhibited reduced perivascular Aqp4 with no redistribution of Aqp4 to the greater astrocyte plasmalemma, while ischemic white matter exhibited increased Aqp4 immunoreactivity at the astrocytic perivascular endfoot, soma, and main processes.

    Conclusions: Distinct patterns of Aqp4 expression and subcellular localization in grey versus white matter astrocytes raise the possibility that cerebral white matter may play a heretofore underappreciated role in the formation of cerebral edema following ischemia.

    Patient Care: Currently used treatments for brain edema, such as decompressive craniectomy and osmotherapy, do not directly target the underlying molecular mechanisms of cerebral edema. By better understanding the roles of key proteins in the generation of cerebral edema, we might rationally develop new strategies for intervention.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of astrocytic water transport in the formation of cerebral edema following ischemic stroke, 2) Understand pertinent physiological differences between white and grey matter astrocytes


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