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

• Published in: Molecular neurobiology 2016-09, Vol.53 (7), p.4865-4873
• Main Authors: Dai, Hai-Bin, Xu, Miao-Miao, Lv, Jia, Ji, Xiang-Jun, Zhu, Si-Hai, Ma, Ru-Meng, Miao, Xiao-Lei, Duan, Man-Lin
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Biomedical and Life Sciences; Biomedicine; Brain Ischemia - metabolism; Brain Ischemia - pathology; Brain Ischemia - therapy; Cell Biology; Combined Modality Therapy - methods; Disease Models, Animal; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Hydrogen sulfide; Hydrogen Sulfide - administration & dosage; Hypothermia; Hypothermia, Induced - methods; Ischemia; Male; Neurobiology; Neurology; Neurons - drug effects; Neurons - metabolism; Neurosciences; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - metabolism; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - therapy; Resuscitation - methods; Signal Transduction - drug effects; Signal Transduction - physiology; Treatment Outcome
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-015-9391-z

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