Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia
Abstract
Recent evidence suggests that apolipoprotein E (ApoE) plays a role in neurologic disease. This experiment compared the neurologic and histologic outcome of ApoE-deficient mutant and wild-type mice subjected to a 60- or 90-minute episode of middle cerebral artery filament occlusion and a recovery interval of 24 hours. With 60 minutes of ischemia, there was no mortality. Apolipoprotein E-deficient mice had larger infarcts (cortex: ApoE deficient = 20 mm3 +/- 12, wild-type = 9 +/- 7 mm3, P = 0.03; subcortex: ApoE deficient = 22 +/- 7 mm3, wild-type = 16 +/- 7 mm3, P = 0.07). Hemiparesis was less severe in wild-type animals (P = 0.02). After 90 minutes of ischemia, mortality in ApoE-deficient mice (n = 10) was 40% versus 0% in wild-type mice (n = 10; P = 0.09). Intraparenchymal hemorrhage was found in 3 of the 4 dead mice. No difference in cortical (ApoE deficient = 37 +/- 8 mm3; wild-type = 31 +/- 18 mm3; P = 0.49) or subcortical (ApoE deficient = 30 +/- 11 mm3; wild-type = 32 +/- 18 mm3; P = 0.78) infarct volumes was present among survivors. ApoE-deficient mice had a prolonged activated partial thromboplastin time and increased fibrinogen concentration. This data supports the hypothesis that apolipoprotein E plays a role in the pathophysiology of ischemic brain damage.
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ApoE knock-out mice and ε4/4 targeted replacement mice exhibit more severe neurological and cognitive deficits after closed head injury, experimental stroke, entorhinal cortex lesions, and experimental allergic encephalomyelitis than controls.
“apoE knock-out mice and 4/4 targeted replacement mice exhibit more severe neurological and cognitive deficits after closed head injury (Chen et al., 1997;Sabo et al., 2000), experimental stroke (Laskowitz et al., 1997;Sheng et al., 1998Sheng et al., , 1999)), entorhinal cortex lesions (Fagan et al., 1998;White et al., 2001) and experimental allergic encephalomyelitis (Karussis et al., 2003) than”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Laskowitz et al., 1997
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Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
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Delirium: An emerging frontier in the management of critically ill children
Smith, H. A. B., Fuchs, D. C., Pandharipande, P. P., Barr, F. E., & Ely, E. W. (2009) · Critical Care Clinics · doi:10.1016/j.ccc.2009.05.002 · Cited by 87 · see citing works
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Apolipoprotein E Polymorphism: Survival and Neurological Outcome After Cardiopulmonary Resuscitation
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- Authors
- Laskowitz, D. T., Sheng, H., Bart, R. D., Joyner, K. A., Roses, A. D., & Warner, D. S.
- Affiliations
- Duke University (US)
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 1997-07
- Volume
- 17
- Issue
- 7
- Pages
- 753-758
- ISSN
- 0271-678X (ISSN-L)
- OpenAlex
- W1978665911
- Cited by
- 166
- References
- 3
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 9 · 2012: 3
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm039771-13)
- National Institute of General Medical Sciences (R01GM39771)
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- apolipoprotein E, ApoE-deficient mice, focal cerebral ischemia, middle cerebral artery occlusion, cerebral infarct volume, hemiparesis, mortality, intraparenchymal hemorrhage, activated partial thromboplastin time, fibrinogen, ischemic brain injury, neuroprotection
- MeSH terms
- Animals, Apolipoproteins E, Bleeding Time, Cerebral Hemorrhage, Cerebral Infarction, Brain Ischemia, Disease Susceptibility, Male, Reference Values, Reperfusion, Survival Analysis, Mice
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