Abstract | BACKGROUND: METHODS: RESULTS: Endogenous TREM2 expression was increased and peaked at 24 h after ICH. TREM2 was expressed on microglia, astrocytes, and neurons. COG1410 improved both short-term and long-term neurological functions, reduced brain edema, inhibited microglia/macrophage activation and neutrophil infiltration, and suppressed neuronal apoptotic cell death in perihematomal areas after ICH. Knockdown of endogenous TREM2 by TREM2 siRNA aggravated neurological deficits and decreased the expression of TREM2 in naïve and ICH mice. COG1410 was associated with upregulation of TREM2, PI3K, phosphorylated-Akt, and Bcl-2 and downregulation of TNF-α, IL-1β, and Bax after ICH. The neuroprotective effects of COG1410 were abolished by both TREM2 siRNA and PI3K inhibitor LY294002. CONCLUSIONS: Our finding demonstrated that TREM2 activation improved neurological functions and attenuated neuroinflammation and neuronal apoptosis after ICH, which was, at least in part, mediated by activation of PI3K/Akt signaling pathway. Therefore, activation of TREM2 may be a potential therapeutic strategy for the management of ICH patients.
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Authors | Shengpan Chen, Jianhua Peng, Prativa Sherchan, Yongjie Ma, Sishi Xiang, Feng Yan, Hao Zhao, Yong Jiang, Ning Wang, John H Zhang, Hongqi Zhang |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 17
Issue 1
Pg. 168
(May 28 2020)
ISSN: 1742-2094 [Electronic] England |
PMID | 32466767
(Publication Type: Journal Article)
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Chemical References |
- Membrane Glycoproteins
- Receptors, Immunologic
- Trem2 protein, mouse
- Proto-Oncogene Proteins c-akt
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Topics |
- Animals
- Apoptosis
(physiology)
- Cerebral Hemorrhage
(metabolism, pathology)
- Inflammation
(metabolism, pathology)
- Male
- Membrane Glycoproteins
(metabolism)
- Mice
- Neurons
(metabolism, pathology)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Receptors, Immunologic
(metabolism)
- Signal Transduction
(physiology)
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