Mild Hypothermia Combined with Hydrogen Sulfide Treatment During Resuscitation Reduces Hippocampal Neuron Apoptosis Via NR2A, NR2B, and PI3K-Akt Signaling in a Rat Model of Cerebral Ischemia-Reperfusion Injury.
We investigated whether mild hypothermia combined with sodium hydrosulfide treatment during resuscitation improves neuron survival following cerebral ischemia-reperfusion injury beyond that observed for the individual treatments. Male Sprague-Dawley rats were divided into seven groups (n = 20 for each group). All rats underwent Pulsinelli 4-vessel occlusion. Ischemia was induced for 15 min using ligatures around the common carotid arteries, except for the sham group. Immediately after initiating reperfusion, the mild hypothermia (MH), sodium hydrosulfide (NaHS), hydroxylamine (HA), MH + NaHS, MH + HA, and ischemia-reperfusion (I/R) control groups received an intraperitoneal injection of saline, sodium hydrosulfide, hydroxylamine, sodium hydrosulfide, hydroxylamine, and saline, respectively, and mild hypothermia (32 to 33 °C) was induced in the MH, MH + NaHS, and MH + HA groups for 6 h. The levels of NR2A, NR2B, p-Akt, and p-Gsk-3β in the hippocampus of the MH, NaHS, and MH + NaHS groups were higher than those in the I/R control group, with the highest levels observed in the MH + NaHS group (P < 0.05). Treatment with hydroxylamine reduced the levels of these proteins in the HA and MH + HA groups, compared with the I/R control and MH groups, respectively. The apoptotic index of the CA1 region of the hippocampus was 45.2, 66.5, 63.5, and 84.8 % in the MH + NaHS, MH, NaHS, and I/R control groups, respectively (P < 0.05), indicating that the combination treatment shifted the NR2A/NR2B balance in favor of synaptic neuron stimulation and phosphatidylinositol 3'-kinase (PI3K)/Akt signaling. The combination of mild hypothermia and sodium hydrosulfide treatment for resuscitation following ischemia-reperfusion injury was more beneficial for reducing hippocampal apoptosis and pathology than that of mild hypothermia or hydrogen sulfide treatment alone.
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
Hai-Bin
HB
Dai
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
Miao-Miao
MM
Xu
Department of Anaesthesiology, The 117th Hospital of PLA, No.14 Lingyin Road, Hangzhou, 310013, China.
Jia
J
Lv
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
Xiang-Jun
XJ
Ji
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
Si-Hai
SH
Zhu
Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, No. 569 Xinsi Road, Xi'an, 710038, Shaanxi, China. 76113480@qq.com.
Ru-Meng
RM
Ma
Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongren Tiyuchang South Road, Chaoyang District, Beijing, 100020, China. xiaoleimiaoabs@163.com.
Xiao-Lei
XL
Miao
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China. duanmanlinbm@163.com.
Man-Lin
ML
Duan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D012151:Resuscitation / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D006862:Hydrogen Sulfide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
Cerebral resuscitation; Ischemia-reperfusion; Mild hypothermia; NMDARs