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Objective To explore the effects of bone marrow mesenchymal stem cells (MSCs) transplantation on receptor-interacting protein kinase 1 (RIP1) and RIP3 in rat brain after cardiac arrest (CA).Methods Sprague Dawley (SD) rats were randomly (random number) divided into sham group (n=8),CA group (n=8) and MSCs group (n=8).Animals were subjected to asphyxial cardiac arrest and followed by cardiopulmonary resuscitation (CPR).In MSCs group or CA group,animals received intravenous injection of 1 × 106 MSCs in 0.5 mL phosphate buffer solution (PBS) or 0.5 mL PBS alone at 1 h after successful resuscitation.Neurological deficit scores (NDS) were assessed at 3 d after CPR.Donor MSCs in brain were detected under a fluorescent microscope.HE staining of brain tissue was performed to observe necrotic neurons.Western blot analysis was performed to measure the levels of RIP1 and RIP3 in brain.Multiple comparisons were made by analysis of variance or Kruskal-Wallis H test.Results At 3 d after CPR,MSCs group demonstrated higher NDS than CA group [72.5(71.5,73.2) vs.63.0(62.5,64.1),Z=3.376,P=0.001].DAPI-labeled MSCs were primarily observed in the cerebral cortex.The percentage of necrotic neurons in MSCs group was significantly lower than that in CA group [(29.6±5.9)％ vs.(57.2±6.4)％,t=8.922,P＜0.01].The levels of RIP1 and RIP3 expression in brain in MSCs group were significantly lower than those in CA group [RIP1:0.227(0.193,0.243) vs.0.599(0.535,0.629),Z=3.151,P=0.001;RIP3:0.217(0.203,0.274) vs.0.543(0.533,0.555),Z=3.361,P=0.001].Conclusion MSCs transplantation improves neurological function after CPR from CA in rats likely associated with inhibiting necroptosis.
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Objective To investigate the effects of bone marrow mesenchymal stem cells (MSCs)treatment on TSG-6 in a rat model of cardiopulmonary resuscitation (CPR).Methods Sprague Dawley (SD) rats were randomly (random number) divided into sham group,phosphate buffer solution (PBS)-treated group and MSCs-treated group.Animals were subjected to asphyxial cardiac arrest followed by CPR.In PBS-treated group or MSCs-treated group,animals were injected intravenously with PBS or MSCs at 2h after resuscitation.Neurological deficit scores (NDS) were assessed at 1,3 and 7 d after CPR.Serum S-100B was assayed using enzyme linked immunosorbent assay (ELISA).Immunofluorescence was performed to detect donor MSCs and the expression of TSG-6 in brain.TSG-6 and proinflammatory cytokines in brain were assayed using real time reverse transcription-polymerase chain reaction (RT-PCR).Western blot analysis was performed to measure the levels of neutrophil elastase (NE) in brain.Multiple comparisons were made by analysis of variance.Results At 3d and 7d,MSCs-treated group demonstrated higher NDS than PBS-treated group (P ＜ 0.01),and serum S-100B levels significantly reduced in MSCs-treated group compared with PBS-treated group (P ＜ 0.01).DAPI-labeled MSCs migrated into the ischemic brain and some DAPI + cells colocalized with TSG-6.Compared with PBS-treated group,MSCs treatment significantly up-regulated the expression of TSG-6 and reduced the expression of NE and proinflammatory cytokines in brain at 3 d and 7 d after CPR (P ＜ 0.05).Conclusion Systemically administered MSCs suppressed inflammatory responses in brain after CPR and improved neurological function in rats possibly via induction of TSG-6.
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Objective To investigate the effects of hydrogen on post - cardiac arrest brain injury in rabbits.Method Sixty New Zealand rabbits were randomly divided into two groups,namely experiment group ( group A,n =30 ) and control group ( group B,n =30 ).Inhalation of 2％ hydrogen gas was conferred to rabbits immediately at the end of cardiac arrest modeling for 72 hours in the group A. Air instead was given to rabbits in the group B.Blood samples were collected before cardiac arrest (CA),and 4,12,24 and 72 hours after restoration of spontaneous circulation (ROSC) in all rabbits for determining the levels of hydrogen,tumor necrosis factor - α ( TNF - α),neuron - specific enolase (NSE) and protein S100β.At the same time,rectal temperature,mean arterial pressure,heart rate and respiration rate were recorded,and the neurologic deficit scoring (NDS) was carried out.The rate of systemic inflammatory response syndrome ( SIRS ) and the rate of survival of rabbits were analyzed. Results There was no significant difference in level of TNF - α activation between group A and group B within12 h of cardiopulmonary resuscitation (CPR).In group A,TNF - α level and the rate of SIRS peaked at 24 hours after CPR,which were higher than those in group B,and then decreased gradually,and the rate of survival was higher than that in group B in 72 hours after ROSC,the NSE was lower than that in group B at 24 hours after ROSC.In group B,S100β level began to increase significantly 4 hours after CPR,which was higher than that in group A,the level of NDS in group B was higher than that in group A 72 hours after ROSC.Conclusions Inhalation of hydrogen gas lessened inflammation and alleviated the brain injury after CPR.
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OBJECTIVE:To study the influence of different doses of naloxone on focal cerebral ischemia reperfusion injury in rats and to explore its mechanism.METHODS:The rats were randomly divided into the sham operation group,the model group,the naloxone group(high dosage,moderate dosage,and low dosage)and the positive control group.The modified Longa method was applied to establish the models of focal cerebral ischemia reperfusion in rats.Infarct size,neurological deficit scores,superoxide dismutase(SOD)activity,malondialdehyde(MDA)content in serum of the model rats were detected.The ultrastructures of the brain tissues were observed by electron microscopy.RESULTS:Ischemia reperfusion injury in model rats resulted in increased neurological deficit scores,larger infarct size,decreased activity of SOD in serum and increased content of MDA.The pathological change and ultrastructural change were evident.The above indices were improved in all the groups administered with different doses of naloxone.CONCLUSIONS:Naloxone has protective effects on rat brain injury caused by focal cerebral ischemia reperfusion,whose mechanism might be related to inhibition of lipid peroxidation.