Curcumin Attenuates Hypoxic-Ischemic Brain Injury in Neonatal Mice Through Inhibition of HMGB1 Acetylation-Mediated Inflammation

To date, there is still no specific treatment for neonatal hypoxic-ischemic encephalopathy and new therapies are urgently needed. The excessive neuroinflammatory response activated by hypoxia-ischemia plays an important role in the occurrence and exacerbation of hypoxic-ischemic brain injury in neonates. Metabolites extracted from plants exhibit positive anti-inflammatory effects, among which curcumin has been demonstrated to have powerful anti-inflammatory, antioxidant, and antitumor effects. In the present study, we explored the potential mechanisms by which curcumin protects against hypoxic-ischemic brain injury. On postnatal day 7, mice were randomly divided into three groups: the sham group, the HI+PBS group, and the HI+curcumin group. Curcumin (200 mg/kg) was administered to mice in the HI+curcumin group by intraperitoneal injection. The hypoxic-ischemic brain injury model was established by the Rice-Vannucci method, and the neuroprotective effects as well as the underlying mechanisms of curcumin on neonatal hypoxic-ischemic brain injured mice were analyzed using a neurobehavioral test (i.e., Morris water maze), 2,3,4-triphenyltetrazolium chloride staining, quantitative real-time polymerase chain reaction, and western blot methods. Curcumin inhibited hypoxia-ischemia insult-induced neurobehavioral deficits, cerebral infarction, and abnormal inflammatory responses in neonatal mice and further downregulated the acetylation level of the high-mobility group protein B1. In conclusion, curcumin attenuated hypoxic-ischemic brain injury in neonatal mice by inhibiting the neuroinflammatory response mediated by acetylation modification of HMGB1, thus providing a new theoretical basis for curcumin as a treatment for neonatal hypoxic-ischemic encephalopathy.