Hypothermia exerts early neuroprotective effects involving protein conjugation of SUMO-2/3 in a rat model of middle cerebral artery occlusion

How hypothermia serves an early protective role against cerebral ischemia remains to be determined. The small ubiquitin-related modifier protein (SUMO) functions as a post-translational modification system and SUMO-2/3 subtypes are often activated in early stress. The present study investigated changes in the protein level of SUMO using western blotting and immunocytochemistry when neurons were exposed to oxygen-glucose deprivation (OGD) in vitro, as well as in a rat model of middle cerebral artery occlusion (MCAO) in vivo. The results demonstrated that a large number of proteins were conjugated to SUMO-2/3 in OGD-injured neurons (within 10 min, peaking at 12 h), and was markedly enhanced under conditions of hypothermia (33°C). Concordantly, lactate dehydrogenase (LDH) release and the apoptosis rate, as determined by LDH and TUNEL assays, respectively, were lower in hypothermia-treated neurons. Similar results were obtained in a rat model of MCAO. Neurological deficit scores were lower in the hypothermia group than in the sham group in the early stage of cerebral ischemia (P<0.05). However, no significant differences in neurological deficit scores were detected between the hypothermia group and the sham group in the late stage of ischemia (21 days; P>0.05). This study implicates a role for SUMO-2/3 in early hypothermia-induced neuroprotection against stroke. The development of small molecule therapeutics based on SUMO-2/3 may benefit patients with cerebral ischemia.