Chipmunk Brain Is Resistant to Injury from Deep Hypothermic Circulatory Arrest During Cardiopulmonary Bypass

花栗鼠的大脑能够抵抗心肺旁路手术期间深低温循环停止造成的损伤

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作者:Xuan Jiang, Tianxiang Gu, Yu Liu, Shilun Gao, Enyi Shi, Guangwei Zhang

Abstract

Chipmunk as a food-storing hibernator naturally undergoes hibernation that is linked to great changes in systemic physiology and could protect the central nervous system during drastically reduced cerebral blood flow and low temperature in hibernation. Deep hypothermic circulatory arrest (DHCA) is associated with neurological dysfunction. We aim to test whether the euthermic chipmunk is resistant to injury from DHCA. Sprague-Dawley (SD) rats were used in a positive control. Ten euthermic chipmunks and 10 rats were subjected to 60-minute DHCA. Sham rats and chipmunks received cannulations. The blood samples after surgery were extracted to measure the tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) level. The levels of opioid receptor delta 1 (OPRD1), mature brain-derived neurotrophic factor (m-BDNF), precursor of BDNF (pro-BDNF), TrkB, GRB2, Erk, p-Erk, P38, Bcl-2, P75NTR, TRAF6, JNK, P53, Bax, and Caspase3 of the hippocampus were analyzed at 24 hours after surgery. The brain of chipmunks and rats were fixed for histopathological assessment. In the DHCA rat group, the levels of TNF-α and IL-6 were greater (p < 0.05) compared with DHCA chipmunks. In the DHCA chipmunk group, the levels of OPRD1, mature BDNF/pro-BDNF, TrkB-FL/TrkB-T1, Bcl-2, and p-Erk/Erk of hippocampus were higher than DHCA rats. The levels of GRB2, P75NTR, TRAF6, P53, Bax, and Caspase3 in DHCA chipmunks were lower than DHCA rats. The histopathological assessment showed that the injury in DHCA rat group was more severe than the DHCA chipmunk group. Euthermic chipmunks were greatly tolerant to global cerebral injury during DHCA. Different isoforms of BDNF might be involved in the resistant strategy.

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