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Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage.

Publication ,  Journal Article
James, ML; Sullivan, PM; Lascola, CD; Vitek, MP; Laskowitz, DT
Published in: Stroke
February 2009

BACKGROUND AND PURPOSE: The purpose of the study was to evaluate the effect of APOE genotype and the feasibility of administering an apolipoprotein E-mimetic therapeutic to modify outcomes in a murine model of intracerebral hemorrhage. METHODS: Intracerebral hemorrhage was induced via stereotactic injection of 0.1 U Clostridial collagenase into the left basal ganglia of wild-type and apolipoprotein-E targeted-replacement mice, consisting of either homozygous 3/3 or 4/4 genotypes. Animals were randomized to receive either vehicle or apolipoprotein E-mimetic peptide. Outcomes included functional neurological tests (21-point neuroseverity score and Rotorod latency) over the initial 7 days after injury, radiographic and histological hemorrhage size at 3 and 7 days, brain water content for cerebral edema at 24 hours, and quantitative polymerase chain reaction for inflammatory markers at 6, 24, and 48 hours. RESULTS: Apolipoprotein-E targeted-replacement mice consisting of homozygous 3/3 demonstrated superior neuroseverity scores and Rotorod latencies over the first 3 days after intracerebral hemorrhage, decreased cerebral edema at 24 hours, and reduced upregulation of IL-6 and endothelial nitric oxide synthase at 6 hours when compared to their apolipoprotein-E targeted-replacement mice consisting of homozygous 4/4 counterparts. After intravenous administration of 1 mg/kg apolipoprotein E-mimetic peptide, both wild-type and apolipoprotein-E targeted-replacement mice consisting of homozygous 4/4 exhibited improved functional outcomes over 7 days after intracerebral hemorrhage, less edema at 24 hours, and reduced upregulation of IL-6 and endothelial nitric oxide synthase when compared to mice that did not receive the peptide. CONCLUSIONS: Our data indicate that APOE genotype influences neurological outcome after intracerebral hemorrhage in a murine model. In particular APOE4 is associated with poor functional outcome and increased cerebral edema. Additionally, this outcome can be modified by the addition of an apolipoprotein E mimetic-peptide, COG1410.

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Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

February 2009

Volume

40

Issue

2

Start / End Page

632 / 639

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Stereotaxic Techniques
  • Reverse Transcriptase Polymerase Chain Reaction
  • Postural Balance
  • Polymorphism, Genetic
  • Pharmacogenetics
  • Peptides
  • Neurology & Neurosurgery
  • Nervous System Diseases
  • Microinjections
 

Citation

APA
Chicago
ICMJE
MLA
NLM
James, M. L., Sullivan, P. M., Lascola, C. D., Vitek, M. P., & Laskowitz, D. T. (2009). Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage. Stroke, 40(2), 632–639. https://doi.org/10.1161/STROKEAHA.108.530402
James, Michael L., Patrick M. Sullivan, Christopher D. Lascola, Michael P. Vitek, and Daniel T. Laskowitz. “Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage.Stroke 40, no. 2 (February 2009): 632–39. https://doi.org/10.1161/STROKEAHA.108.530402.
James ML, Sullivan PM, Lascola CD, Vitek MP, Laskowitz DT. Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage. Stroke. 2009 Feb;40(2):632–9.
James, Michael L., et al. “Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage.Stroke, vol. 40, no. 2, Feb. 2009, pp. 632–39. Pubmed, doi:10.1161/STROKEAHA.108.530402.
James ML, Sullivan PM, Lascola CD, Vitek MP, Laskowitz DT. Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage. Stroke. 2009 Feb;40(2):632–639.

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

February 2009

Volume

40

Issue

2

Start / End Page

632 / 639

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Stereotaxic Techniques
  • Reverse Transcriptase Polymerase Chain Reaction
  • Postural Balance
  • Polymorphism, Genetic
  • Pharmacogenetics
  • Peptides
  • Neurology & Neurosurgery
  • Nervous System Diseases
  • Microinjections