Crocin enhances hypothermia therapy in hypoxic ischemia-induced brain injury in mice

Hypoxic–ischemic encephalopathy (HIE) is a serious medical situation at labor which leads to severe brain damage. Hypothermia therapy is the standard treatment for infants with HIE, but the efficacy is limited. Combination treatments are considered to enhance the efficacy of hypothermia. Crocin is an extract from saffron which has anti-inflammatory, anti-oxidant, and neuroprotective properties. The present study sought to investigate whether crocin could act as a combined treatment with hypothermia in a mouse model of HIE. C57BL/6J mice at post-natal day 7 were subjected to left common carotid artery ligation, followed by treatment of crocin (10 mg/kg) and hypothermia, either alone or in combination. Brain edema and tissue infarct were measured to evaluate brain damage. Mediators involved in inflammatory response and oxidative stress were measured. Neurological severity score test was performed to evaluate the functional outcome. Results show that crocin treatment alone could reduce inflammation and brain damage after hypoxia–ischemia. Combined treatment of crocin and hypothermia exerted enhanced therapeutic effect compared with single treatment, resulting in significantly less brain damage, reduced inflammatory and oxidative responses, and improved functional outcome. Together, these data suggest that crocin plays a beneficial effect in the mouse model of HIE. It could also enhance the neuroprotective effect of hypothermia and might be considered as a combination therapeutic treatment with hypothermia in HIE.