Neurocritical Care

, Volume 4, Issue 1, pp 25–31

A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage

Authors

  • Junling Gao
    • Multidisciplinary Neuroprotection Laboratories the Department ofDuke University Medical Center
    • Department of NeurologyDuke University Medical Center
    • Department of Histology and EmbryologyNorth China Coal Medical College
  • Haichen Wang
    • Multidisciplinary Neuroprotection Laboratories the Department ofDuke University Medical Center
    • Department of NeurologyDuke University Medical Center
  • Huaxin Sheng
    • Multidisciplinary Neuroprotection Laboratories the Department ofDuke University Medical Center
    • AnesthesiologyDuke University Medical Center
  • John R. Lynch
    • Multidisciplinary Neuroprotection Laboratories the Department ofDuke University Medical Center
    • Department of NeurologyDuke University Medical Center
  • David S. Warner
    • Multidisciplinary Neuroprotection Laboratories the Department ofDuke University Medical Center
    • NeurobiologyDuke University Medical Center
    • AnesthesiologyDuke University Medical Center
  • Lori Durham
    • Department of NeurologyDuke University Medical Center
  • Michael P. Vitek
    • Department of NeurologyDuke University Medical Center
    • NeurobiologyDuke University Medical Center
    • Cognosci Inc.
    • Multidisciplinary Neuroprotection Laboratories the Department ofDuke University Medical Center
    • Department of NeurologyDuke University Medical Center
    • NeurobiologyDuke University Medical Center
    • AnesthesiologyDuke University Medical Center
Translational Research

DOI: 10.1385/NCC:4:1:025

Cite this article as:
Gao, J., Wang, H., Sheng, H. et al. Neurocrit Care (2006) 4: 25. doi:10.1385/NCC:4:1:025

Abstract

Introduction

Recent clinical observations demonstrate that the APOE4 genotype increases the development of delayed ischemic deficit and worsens prognosis following aneurysmal subarachnoid hemorrhage (SAH). In the current study, we use targeted replacement mice expressing only human apoE3 or apoE4 to model the isoform-specific effects of apoE following SAH. We then test the hypothesis that an apoE-derived therapeutic peptide reduces vasospasm and improves functional recovery after SAH.

Methods

Experimental SAH was induced in APOE3- and APOE4-targeted replacement mice. For 3 days following injury, daily functional assessments were made. Mice were then sacrificed and the cerebral vasculature visualized to quantify vasospasm. In a separate experiment, C57BI/6 mice were treated with intravenous injection of vehicle, low-dose, or high-dose apoE-mimetic peptide every 12 hours for 3 days post-SAH. Functional endopoints were assessed on a daily basis, followed by measurement of middle cerebral artery diameter.

Results

Mice expressing the apoE4 isoform had greater functional deficit, mortality, cerebral edema, and vasospasm as compared with their apoE3 counterparts. Mice treated with the apoE-mimetic peptide had decreased mortality, functional deficits, and histological evidence of vasospasm as compared with vehicle-treated animals.

Conclusion

Consistent with the clinical literature, the apoE4 isoform is associated with an increased incidence of vasospasm and poor functional recovery after experimental SAH. An apoE-derived peptide represents a novel therapeutic approach for the treatment of SAH.

Key Words

Subarachnoid hemorrhageapolipoprotein Einflammationvasospasm
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Copyright information

© Humana Press Inc. 2006