Brain Hypothermic Therapy Dramatically Decreases Elevated Blood Concentrations of High Mobility Group Box 1 in Neonates with Hypoxic-Ischemic Encephalopathy

Abstract

Background. According to the Consensus 2010 of the International Liaison Committee on Resuscitation (ILCOR), children with moderate to severe hypoxic-ischemic encephalopathy (HIE) should receive brain hypothermic therapy (BHT) after successful resuscitation. Elevated high mobility group box 1 (HMGB1) in the blood at the early stage of brain ischemia-reperfusion injury has been suggested to be involved in the release of various inflammatory cytokines. Methods. In total, 21 neonates plasma HMGB1 concentration was measured. These neonates included 8 with HIE in whom BHT was indicated, 5 controls diagnosed as having HIE but who were not suitable candidates for BHT, and 8 normal controls. Results. The umbilical artery HMGB1 (UA-HMGB1) level before undergoing BHT significantly exceeded reference values. The UA-HMGB1 level in the BHT (−) group did not differ significantly from reference values, but was significantly increased 24 hours after birth. Repeated measure ANOVA showed a significant difference in time course changes between the BHT (+) and BHT (−) groups (P = 0.0002). Conclusions. This study demonstrated hypothermic therapy to significantly decrease HMGB1. Furthermore, HMGB1 is a useful index of the inhibition of early stage inflammation.

Brain-immune interactions in perinatal hypoxic-ischemic brain injury

“…A line of evidence supports this hypothesis that the levels of HMGB1 are significantly lower in the blood of HIE infants treated with TH compare to that of untreated HIE infants (Nakamura et al , 2013). The activation of Janus kinase 2/STAT3 signaling pathway mediated by IL-6 results in expression of a series of genes involved in inflammation and apoptosis.…”

A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat

“…It has been reported that cerebral ischemia can upregulate serum HMGB1 to stimulate the release of TNFα, IL-6, and other inflammatory factors to induce inflammation, which will contribute to cerebral ischemic injury (Yang et al 2010). Certain HMGB1 inhibitors or some physical methods can attenuate injuries caused by cerebral ischemia reperfusion or neonatal hypoxic-ischemic encephalopathy (Nakamura et al 2013;Rickenbacher et al 2014;Wang et al 2012). Furthermore, previous studies have suggested that there would be a certain relationship between HMGB1 and autophagy (Kang et al 2011;Thorburn et al 2009).…”

High Mobility Group Box 1 in Children with Acute Encephalopathy and Other Convulsive Diseases

“…Production of MMP-916) and free radicals [17,18] and resulting damage to the BBB [19] has been reported to be the pathophysiology in acute encephalopathy. HMGB1 is also a good marker to help predict the outcome in neurological damage [20,21].…”