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Apolipoprotein E modulates the CNS response to injury

Publication ,  Journal Article
Laskowitz, DT; Lynch, JR; Warner, DS; Pineda, J
Published in: Journal of Neurochemistry
June 2002

Apolipoprotein E (apoE) plays an important role in recovery from acute brain injury. One potential mechanism for this is that apoE down‐regulates glial activation and subsequent secretion of inflammatory mediators. Following a pneumatic impact to the closed skull of anesthetized apoE deficient and wildtype mice, MRI was performed to quantify the effacement of the lateral ventricles as a radiographic surrogate for cerebral edema. At 24 hours following injury, apoE deficient animals had a greater degree of cerebral edema as compared to matched controls. This increase in edema was associated with enhanced up‐regulation of TNFα, a pro‐inflammatory cytokine believed to play an important role in mediating blood–brain barrier breakdown and the development of cerebral edema. We have previously demonstrated that a peptide derived from the receptor binding region of apoE retained the anti‐inflammatory activities of the holoprotein , and we next investigated whether a single intravenous administration of this apoE‐mimetic peptide could exert neuroprotective effects. Thirty minutes after closed head injury, mice were randomized to receive low dose peptide (203 mg/kg); high dose peptide (406 mg/kg), or vehicle. At 24 h post injury, the saline injected animals had a profound deficit in rotorod testing which was associated with weight loss. A single intravenous injection of apoE‐mimetic peptide 30 min following closed head injury protected against motor deficit, weight loss, and neurocognitive deficit in a dose dependent fashion. This suggests that apoE may modify prognosis in brain injury by down‐regulating the CNS inflammatory response, and that mimicking the biological activity of apoE may lead to novel therapeutic strategies in the setting.

Duke Scholars

Published In

Journal of Neurochemistry

DOI

EISSN

1471-4159

ISSN

0022-3042

Publication Date

June 2002

Volume

81

Issue

s1

Start / End Page

31 / 31

Publisher

Wiley

Related Subject Headings

  • Neurology & Neurosurgery
  • 3209 Neurosciences
  • 3101 Biochemistry and cell biology
  • 1109 Neurosciences
  • 0601 Biochemistry and Cell Biology
 

Citation

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Laskowitz, D. T., Lynch, J. R., Warner, D. S., & Pineda, J. (2002). Apolipoprotein E modulates the CNS response to injury. Journal of Neurochemistry, 81(s1), 31–31. https://doi.org/10.1046/j.1471-4159.81.s1.74.x
Laskowitz, D. T., J. R. Lynch, D. S. Warner, and J. Pineda. “Apolipoprotein E modulates the CNS response to injury.” Journal of Neurochemistry 81, no. s1 (June 2002): 31–31. https://doi.org/10.1046/j.1471-4159.81.s1.74.x.
Laskowitz DT, Lynch JR, Warner DS, Pineda J. Apolipoprotein E modulates the CNS response to injury. Journal of Neurochemistry. 2002 Jun;81(s1):31–31.
Laskowitz, D. T., et al. “Apolipoprotein E modulates the CNS response to injury.” Journal of Neurochemistry, vol. 81, no. s1, Wiley, June 2002, pp. 31–31. Crossref, doi:10.1046/j.1471-4159.81.s1.74.x.
Laskowitz DT, Lynch JR, Warner DS, Pineda J. Apolipoprotein E modulates the CNS response to injury. Journal of Neurochemistry. Wiley; 2002 Jun;81(s1):31–31.
Journal cover image

Published In

Journal of Neurochemistry

DOI

EISSN

1471-4159

ISSN

0022-3042

Publication Date

June 2002

Volume

81

Issue

s1

Start / End Page

31 / 31

Publisher

Wiley

Related Subject Headings

  • Neurology & Neurosurgery
  • 3209 Neurosciences
  • 3101 Biochemistry and cell biology
  • 1109 Neurosciences
  • 0601 Biochemistry and Cell Biology