Mild
therapeutic hypothermia, a robust
neuroprotectant, reduces neuronal apoptosis, but the precise mechanism is not well understood. Our previous study showed that a novel inhibitor of an apoptosis-stimulating
protein of p53 (iASPP) might be involved in neuronal death after
stroke. The aim of this study was to confirm the role of iASPP after
stroke treated with mild
therapeutic hypothermia. To address this, we mimicked
ischemia/reperfusion injury in vitro by using
oxygen-
glucose deprivation/reperfusion (OGD/R) in primary rat neurons. In our in vivo approach, we induced
middle cerebral artery occlusion (MCAO) for 60 min in C57/B6 mice. From the beginning of
ischemia, focal mild
hypothermia was applied for two hours. To evaluate the role of iASPP,
small interfering RNA (
siRNA) was injected intracerebroventricularly. Our results showed that mild
therapeutic hypothermia increased the expression of iASPP and decreased the expression of its targets, Puma and Bax, and an apoptosis marker, cleaved
caspase-3, in primary neurons under OGD/R. Increased iASPP expression and decreased ASPP1/2 expression were observed under
hypothermia treatment in MCAO mice. iASPP
siRNA (iASPPi) or
hypothermia plus iASPPi application increased
infarct volume, apoptosis and aggravated the neurological deficits in MCAO mice. Furthermore, iASPPi downregulated iASPP expression, and upregulated the expression of proapoptotic effectors, Puma, Bax and cleaved
caspase-3, in mice after
stroke treated with mild
therapeutic hypothermia. In conclusion, mild
therapeutic hypothermia protects against
ischemia/reperfusion
brain injury in mice by upregulating iASPP and thus attenuating apoptosis. iASPP may be a potential target in the
therapy of
stroke.