Dexrazoxane Attenuates Blood-Brain Barrier Injury During Venoarterial Extracorporeal Membrane Oxygenation

Intracerebral hemorrhage during extracorporeal membrane oxygenation (ECMO) is one of the main causes of death and disability, with blood-brain barrier (BBB) disruption playing a key role. Dexrazoxane (DEX) is a Food and Drug Administration (FDA)-approved cardioprotective agent and iron chelator. The aim of this study was to investigate the effect of dexrazoxane on the BBB during venoarterial ECMO (VA ECMO). Rats were randomized into the control group (Con), the VA ECMO group, and the dexrazoxane combined with VA ECMO group (VA ECMO + DEX) (n = 6 per group). We observed brain injury and disruption of the BBB during VA ECMO. Compared with the VA ECMO group, dexrazoxane treatment mitigated brain injury, reduced pathological scores, decreased albumin leakage, and preserved tight junction protein expression. Combined with the assessment of brain tissue iron content, VA ECMO + DEX group had lower total iron, Fe2+ and ptgs2 levels than VA ECMO group. These findings suggest that dexrazoxane may attenuate BBB damage during VA ECMO by down-regulating iron deposition-induced ferroptosis.