Journal of Biological Research - Thessaloniki (May 2022)
Mild hypothermia protects against cerebral oxidative stress injury by regulating endoplasmic reticulum stress in rats after cardiopulmonary resuscitation
Abstract
Oxidative stress injury (OSI) is involved in brain injury induced by cardiac arrest (CA)/cardiopulmonary resuscitation (CPR), and endoplasmic reticulum stress (ERS) is closely related to OSI. Mild hypothermia (MT) has been used to treat different kinds of brain injury but the mechanism remains unclear. Therefore, this study aimed to examine the effects of MT on OSI in a rat model of CA/CPR and determine the relationship between MT and ERS. The rats were divided into the sham, non-hypothermia (NT), and MT groups, which were then each divided into two subgroups consisting of rats that were sacrificed at 4.5 h and 24 h after the return of spontaneous circulation, respectively (NT-4.5, NT-24, MT-4.5, and MT-24 subgroups) (n = 6). A CA/CPR model was established by asphyxiation in the NT and MT groups, and MT was administered to rats in the MT group. Roughly 73% (24/33) of the rats survived until the end of the study. Compared with the sham group, the neurological deficit score (NDS) decreased, and the OSI, apoptosis, water content increased after model establishment (p lower than 0.05). Compared with those in the NT-4.5 and NT-24 groups, rats in the MT-4.5 and MT-24 groups showed improved NDS (65.3 ± 5.1 vs. 52.8 ± 4.7; 59.7 ± 6.0 vs. 50.5 ± 5.4), lower MDA activity (4.7 ± 0.3 vs. 6.5 ± 0.6; 5.1 ± 0.4 vs. 7.7 ± 0.6) (nmol mg-1 protein), higher SOD (84.7 ± 5.2 vs. 67.4 ± 5.8; 73.9 ± 6.4 vs. 55.8 ± 4.1) (U mg-1 protein) and CAT activities (83.1 ± 6.9 vs. 77.2 ± 6.5; 71.9 ± 3.6 vs. 62.7 ± 4.9) (U mg-1 protein), lower water content (79.2 ± 1.1% vs. 80.6 ± 0.8%; 81.0 ± 0.9% vs. 83.7 ± 1.7%), and lower expression of the ERS-related proteins GRP78, CHOP, caspase-12, and cleaved-caspase-3 (p lower than 0.05). The results also showed that after the MT was stopped, the effects were maintained for a period of time. In conclusion, MT protected against brain injury induced by CA/CPR by decreasing OSI by inhibiting of ERS.
Keywords