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

Amin Mottahedin; Pernilla Svedin; Syam Nair; Carl-Johan Mohn; Xiaoyang Wang; Henrik Hagberg; Joakim Ek; Carina Mallard

doi:10.1177/0271678X17691292

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

Amin Mottahedin, Pernilla Svedin, Syam Nair, Carl-Johan Mohn, Xiaoyang Wang, Henrik Hagberg, Joakim Ek, Carina Mallard

Perinatal Imaging & Health

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Abstract

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.

Original language	English
Article number	28139935
Pages (from-to)	1-7
Number of pages	7
Journal	Journal of Cerebral Blood Flow and Metabolism
Early online date	31 Jan 2017
DOIs	https://doi.org/10.1177/0271678X17691292
Publication status	E-pub ahead of print - 31 Jan 2017

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Mottahedin, A., Svedin, P., Nair, S., Mohn, C.-J., Wang, X., Hagberg, H., Ek, J., & Mallard, C. (2017). Systemic activation of Toll-like receptor 2 suppresses mitochondrial respiration and exacerbates hypoxic-ischemic injury in the developing brain. Journal of Cerebral Blood Flow and Metabolism, 1-7. Article 28139935. Advance online publication. https://doi.org/10.1177/0271678X17691292

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abstract = "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.",

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AU - Nair, Syam

AU - Mohn, Carl-Johan

AU - Wang, Xiaoyang

AU - Hagberg, Henrik

AU - Ek, Joakim

AU - Mallard, Carina

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AB - 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.

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

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