Mild hypothermia protects neurons against oxygen glucose deprivation via poly (ADP-ribose) signaling.

ABSTRACT

OBJECTIVE: Hypothermia is a neuroprotective mechanism that has been validated for use in alleviating neonatal hypoxic-ischemic (HI) brain injury. Nevertheless, it is unclear whether poly (ADP-ribose) (PAR) signaling is involved in hypothermia-induced neuroprotection. In this study, we investigated whether mild hypothermia rescues oxygen glucose deprivation (OGD)-induced cell death by modifying PAR-relative protein expression, such as AIF, PARP-1, and PAR polymer, in primary-cultured hippocampal neurons. METHODS: We analyzed neuronal morphology and related protein expression of PAR signaling after OGD followed by mild hypothermia in primary-cultured newborn hippocampal neurons. RESULTS: Hypothermic treatment resulted in improved neuronal viability and alleviated DNA damage. Results from the protein assay showed that hypothermia attenuated nuclear translocation of apoptosis-inducing factor (AIF), inhibited overactivation of poly(ADP-ribose) polymerase-1 (PARP-1), and decreased production of PAR polymer induced by PARP-1 activation after OGD. CONCLUSIONS: These results showed that mild hypothermia partially protects immature hippocampal neurons against OGD injury in part by interfering with the PAR signaling pathway.