Systemic activation of Toll-like receptor 2 suppresses mitochondrial respiration and exacerbates hypoxic–ischemic injury in the developing brain. Issue 4 (April 2017)

• Record Type: Journal Article
• Authors: Mottahedin, Amin; Svedin, Pernilla; Nair, Syam; Mohn, Carl-Johan; Wang, Xiaoyang; Hagberg, Henrik; Ek, Joakim; Mallard, Carina
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 37:Issue 4(2017)
• Page Start: 1192
• Page End: 1198
• Publication Date: 2017-04
• Subjects: Cerebral palsy -- birth asphyxia -- metabolism -- perinatal brain injury; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X17691292
• Languages: English
• ISSNs: 0271-678X

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.