Systemic activation of Toll-like receptor 2 suppresses mitochondrial respiration and exacerbates hypoxic-ischemic injury in the developing brain

被引：29

作者：

Mottahedin, Amin ^{[1
]}

Svedin, Pernilla ^{[1
]}

Nair, Syam ^{[1
]}

Mohn, Carl-Johan ^{[1
]}

Wang, Xiaoyang ^{[1
]}

Hagberg, Henrik ^{[2
,3
]}

Ek, Joakim ^{[1
]}

Mallard, Carina ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden

[2] Kings Coll London, St Thomas Hosp, Div Imaging Sci & Biomed Engn, Ctr Dev Brain,Kings Hlth Partners, London, England

[3] Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynecol, Perinatal Ctr, Gothenburg, Sweden

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2017年 / 37卷 / 04期

基金：

瑞典研究理事会;

关键词：

Cerebral palsy; birth asphyxia; metabolism; perinatal brain injury; INFLAMMATION; TLR2; SENSITIZATION; INCREASES; RESPONSES; GLUTAMATE;

D O I：

10.1177/0271678X17691292

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Infection and inflammation are known risk factors for neonatal brain injury. Mycoplasma and Gram-positive bacteria, for which Toll-like receptor 2 (TLR2) plays a key role in recognition and inflammatory response, are among the most common pathogens in the perinatal period. Here, we report that systemic activation of TLR2 by Pam3CSK4 (P3C) increases neural tissue loss and demyelination induced by subsequent hypoxia-ischemia (HI) in neonatal mice. High-resolution respirometry of brain isolated mitochondria revealed that P3C suppresses ADP-induced oxidative phosphorylation, the main pathway of cellular energy production. The results suggest that infection and inflammation might contribute to HI-induced energy failure.

引用

页码：1192 / 1198

页数：7

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