Transient Global Ischemia-Induced Brain Inflammatory Cascades Attenuated By Targeted Temperature Management

Sudden cardiac arrest leads to a significantly increased risk of severe neurological impairment and higher mortality rates in survivors due to global brain tissue injury caused by prolonged whole-body ischemia and reperfusion. The brain undergoes various deleterious cascading events. Among these damaging mechanisms, neuroinflammation plays an especially crucial role in the exacerbation of brain damage. Clinical guidelines indicate that 33 degrees C and 36 degrees C are both beneficial for targeted temperature management (TTM) after cardiac arrest. To clarify the mechanistic relationship between TTM and inflammation in transient global ischemia (TGI) and determine whether 36 degrees C produces a neuroprotective effect comparable to 33 degrees C, we performed an experiment using a rat model. We found that TTM at 36 degrees C and at 33 degrees C attenuated neuronal cell death and apoptosis, with significant improvements in behavioral function that lasted for up to 72 h. TTM at 33 degrees C and 36 degrees C suppressed the propagation of inflammation including the release of high mobility group box 1 from damaged cells, the activation and polarization of the microglia, and the excessive release of activated microglia-induced inflammatory cytokines. There were equal neuroprotective effects for TTM at 36 degrees C and 33 degrees C. In addition, hypothermic complications and should be considered safe and effective after cardiac arrest.