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
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
收藏
页码:1192 / 1198
页数:7
相关论文
共 27 条
[1]   Perinatal asphyxia in the term newborn [J].
Antonucci, Roberto ;
Porcella, Annalisa ;
Pilloni, Maria Dolores .
JOURNAL OF PEDIATRIC AND NEONATAL INDIVIDUALIZED MEDICINE, 2014, 3 (02)
[2]   Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development [J].
Du, Xiaonan ;
Fleiss, Bobbi ;
Li, Hongfu ;
D'angelo, Barbara ;
Sun, Yanyan ;
Zhu, Changlian ;
Hagberg, Henrik ;
Levy, Ofer ;
Mallard, Carina ;
Wang, Xiaoyang .
PLOS ONE, 2011, 6 (05)
[3]   Bacterial endotoxin sensitizes the immature brain to hypoxic-ischaemic injury [J].
Eklind, S ;
Mallard, C ;
Leverin, AL ;
Gilland, E ;
Blomgren, K ;
Mattsby-Baltzer, I ;
Hagberg, H .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2001, 13 (06) :1101-1106
[4]   Lipopolysaccharide induces both a primary and a secondary phase of sensitization in the developing rat brain [J].
Eklind, S ;
Mallard, C ;
Arvidsson, P ;
Hagberg, H .
PEDIATRIC RESEARCH, 2005, 58 (01) :112-116
[5]   Medical progress - Neonatal brain injury [J].
Ferriero, DM .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (19) :1985-1995
[6]   Inflammation-induced sensitization of the brain in term infants [J].
Fleiss, Bobbi ;
Tann, Cally J. ;
Degos, Vincent ;
Sigaut, Stephanie ;
Van Steenwinckel, Juliette ;
Schang, Anne-Laure ;
Kichev, Anton ;
Robertson, Nicola J. ;
Mallard, Carina ;
Hagberg, Henrik ;
Gressens, Pierre .
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY, 2015, 57 :17-28
[7]   Perinatal brain damage: The term infant [J].
Hagberg, Henrik ;
Edwards, A. David ;
Groenendaal, Floris .
NEUROBIOLOGY OF DISEASE, 2016, 92 :102-112
[8]   The role of inflammation in perinatal brain injury [J].
Hagberg, Henrik ;
Mallard, Carina ;
Ferriero, Donna M. ;
Vannucci, Susan J. ;
Levison, Steven W. ;
Vexler, Zinaida S. ;
Gressens, Pierre .
NATURE REVIEWS NEUROLOGY, 2015, 11 (04) :192-208
[9]   Mitochondria: hub of injury responses in the developing brain [J].
Hagberg, Henrik ;
Mallard, Carina ;
Rousset, Catherine I. ;
Thornton, Claire .
LANCET NEUROLOGY, 2014, 13 (02) :217-232
[10]   Preconditioning with a TLR2 specific ligand increases resistance to cerebral ischemia/reperfusion injury [J].
Hua, Fang ;
Ma, Jing ;
Ha, Tuanzhu ;
Kelley, Jim ;
Williams, David L. ;
Kao, Race L. ;
Kalbfleisch, John H. ;
Browder, I. William ;
Li, Chuanfu .
JOURNAL OF NEUROIMMUNOLOGY, 2008, 199 (1-2) :75-82