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Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice.

Publication ,  Journal Article
Pang, J; Peng, J; Matei, N; Yang, P; Kuai, L; Wu, Y; Chen, L; Vitek, MP; Li, F; Sun, X; Zhang, JH; Jiang, Y
Published in: Transl Stroke Res
December 2018

Subarachnoid hemorrhage (SAH) is a neurologically destructive stroke in which early brain injury (EBI) plays a pivotal role in poor patient outcomes. Expanding upon our previous work, multiple techniques and methods were used in this preclinical study to further elucidate the mechanisms underlying the beneficial effects of apolipoprotein E (ApoE) against EBI after SAH in murine apolipoprotein E gene-knockout mice (Apoe-/-, KO) and wild-type mice (WT) on a C57BL/6J background. We reported that Apoe deficiency resulted in a more extensive EBI at 48 h after SAH in mice demonstrated by MRI scanning and immunohistochemical staining and exhibited more extensive white matter injury and neuronal apoptosis than WT mice. These changes were associated with an increase in NADPH oxidase 2 (NOX2) expression, an important regulator of both oxidative stress and inflammatory cytokines. Furthermore, immunohistochemical analysis revealed that NOX2 was abundantly expressed in activated M1 microglia. The JAK2/STAT3 signaling pathway, an upstream regulator of NOX2, was increased in WT mice and activated to an even greater extent in Apoe-/- mice; whereas, the JAK2-specific inhibitor, AG490, reduced NOX2 expression, oxidative stress, and inflammation in Apoe-deficient mice. Also, apoE-mimetic peptide COG1410 suppressed the JAK2/STAT3 signaling pathway and significantly reduced M1 microglia activation with subsequent attenuation of oxidative stress and inflammation after SAH. Taken together, apoE and apoE-mimetic peptide have whole-brain protective effects that may reduce EBI after SAH via M1 microglial quiescence through the attenuation of the JAK2/STAT3/NOX2 signaling pathway axis.

Duke Scholars

Published In

Transl Stroke Res

DOI

EISSN

1868-601X

Publication Date

December 2018

Volume

9

Issue

6

Start / End Page

654 / 668

Location

United States

Related Subject Headings

  • Tyrphostins
  • Subarachnoid Hemorrhage
  • Signal Transduction
  • Reaction Time
  • Oxidative Stress
  • Neuroprotective Agents
  • Neurologic Examination
  • NADPH Oxidase 2
  • Microglia
  • Mice, Transgenic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pang, J., Peng, J., Matei, N., Yang, P., Kuai, L., Wu, Y., … Jiang, Y. (2018). Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice. Transl Stroke Res, 9(6), 654–668. https://doi.org/10.1007/s12975-018-0665-4
Pang, Jinwei, Jianhua Peng, Nathanael Matei, Ping Yang, Li Kuai, Yue Wu, Ligang Chen, et al. “Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice.Transl Stroke Res 9, no. 6 (December 2018): 654–68. https://doi.org/10.1007/s12975-018-0665-4.
Pang, Jinwei, et al. “Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice.Transl Stroke Res, vol. 9, no. 6, Dec. 2018, pp. 654–68. Pubmed, doi:10.1007/s12975-018-0665-4.
Pang J, Peng J, Matei N, Yang P, Kuai L, Wu Y, Chen L, Vitek MP, Li F, Sun X, Zhang JH, Jiang Y. Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice. Transl Stroke Res. 2018 Dec;9(6):654–668.
Journal cover image

Published In

Transl Stroke Res

DOI

EISSN

1868-601X

Publication Date

December 2018

Volume

9

Issue

6

Start / End Page

654 / 668

Location

United States

Related Subject Headings

  • Tyrphostins
  • Subarachnoid Hemorrhage
  • Signal Transduction
  • Reaction Time
  • Oxidative Stress
  • Neuroprotective Agents
  • Neurologic Examination
  • NADPH Oxidase 2
  • Microglia
  • Mice, Transgenic