Changes in the microglial phenotype drive neuroinflammation independent of systemic inflammation in the acute stage of heatstroke.

Heatstroke causes acute injury and damage across numerous organ systems, during this process, inflammation drives disease progression. In this study, we correlated temporal changes in inflammatory response with barrier breakdown within 24 h following heatstroke onset to explore whether inflammation in circulation can influence inflammation in brain. We found both pro-inflammatory cytokines expression and pathological lesions in tissue were elevated at 1 h and 6 h after heatstroke onset. However, by 24 h after heatstroke onset, while systemic inflammation was sustained at high levels, neuroinflammation and cerebral cortex damage had begun to reverse. The change in microglial phenotype from classic activation at 1 h to alternative activation at 24 h post heatstroke may explain the subsequent abatement of neuroinflammation. Taken together, our results may indicate microglial phenotype transformation drives neuroinflammation independent of systemic inflammation during the acute stage of heatstroke.