No neuroprotective effect of therapeutic hypothermia following lipopolysaccharide-sensitized hypoxia-ischemia: a newborn piglet study

Therapeutic hypothermia is the only proven neuroprotective treatment for hypoxic-ischemic encephalopathy. However, studies have questioned whether therapeutic hypothermia may benefit newborns subjected to infection or inflammation before a hypoxic-ischemic insult. We aimed to compare newborn piglets with lipopolysaccharide-sensitized hypoxia-ischemia treated with and without therapeutic hypothermia with regards to measures of neuroprotection. A total of 32 male and female piglets were included in this randomized experimental study. Lipopolysaccharides from were infused intravenously before initiation of a standardized global hypoxic-ischemic insult. The piglets were then randomized to either normothermia or therapeutic hypothermia. After 14 h, the piglets were evaluated. Our primary outcome was brain lactate/N-acetylaspartate ratio assessed by magnetic resonance spectroscopy. Secondary outcomes included measures of magnetic resonance imaging, amplitude-integrated electroencephalography, immunohistochemistry, and concentration of blood cells and cytokines. Piglets treated with and without therapeutic hypothermia were subjected to comparable global hypoxic-ischemic insults. We found no difference between the two groups with regards to measures of magnetic resonance spectroscopy and imaging, amplitude-integrated electroencephalography, immunohistochemistry, and concentration of blood cells and cytokines. We found no indication of neuroprotection by therapeutic hypothermia in newborn piglets following lipopolysaccharide-sensitized hypoxia-ischemia. However, interpretation of the results is limited by the short observation period. Further studies are required to determine the potential clinical implications of these findings.