Neuroprotective mechanism of autophagy in bradykinin postconditioning after cardiac arrest in rats / 中华危重病急救医学

Objective:To explore the protective effects of bradykinin postconditioning on cardiopulmonary resuscitation (CPR) rats, and to assess the underlying mechanisms.Methods:Forty-eight adult male Sprague-Dawley (SD) rats were randomly divided into four groups according to random number table: Sham operation group, cardiac arrest (CA) group, bradykinin treatment (BK) group, and AMP-activated protein kinase (AMPK) inhibitor Compound C+ bradykinin treatment (CP+BK) group, finally, 8 rats in each group were taken for follow-up experiment. CA was induced by asphyxia. Rats in the Sham group received arteriovenous catheterization, endotracheal intubation, and mechanical ventilation, without CA. Compound C (250 μg/kg) was intraperitoneally injected in CP+BK group 30 minutes before CA, and the same volume of dimethyl sulfoxide (DMSO) was given in the remaining groups. Bradykinin (150 μg/kg) was intraperitoneally injected in BK group and CP+BK group 48 hours after restoration of spontaneous circulation (ROSC), and same volume of saline was given in the remaining groups. The neural function of rats in each group was evaluated with neurological deficit score (NDS) 72 hours after ROSC. Microtubule-associated protein light chain 3 (LC3) and p62 expressions were detected by immunohistochemistry, autophagosomes were observed by transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL) assay was used to assess apoptosis.Results:Compared with the Sham group, the NDS was decreased (60.75±5.80 vs. 80.00±0.00, P < 0.01), the expression levels of LC3 and p62 elevated [LC3 ( A value): 1.04±0.64 vs. 0.40±0.14, p62 ( A value): 2.75±0.57 vs. 0.36±0.12, both P < 0.05], the number of autophagosomes and apoptotic cells increased in the CA group [(39.00±8.00)% vs. (3.87±1.90)%, P < 0.05]. Compared with the CA group, the NDS (67.75±6.32 vs. 60.75±5.80, P < 0.05), the expression of LC3 ( A value: 1.60±0.34 vs. 1.04±0.64, P < 0.05), and the number of autophagosomes increased in the BK group, while the expression of p62 and the rate of apoptotic cells reduced [p62 ( A value): 1.51±0.32 vs. 2.75±0.57, apoptotic cells rate: (23.03±1.91)% vs. (39.00±8.00)%, both P < 0.05]. Compared with the BK group, the NDS (59.00±8.19 vs. 67.75±6.32, P < 0.05), the expression of LC3 ( A value: 0.62±0.41 vs. 1.60±0.34, P < 0.05) and the number of autophagosomes declined in the CP+BK group, while the expression of p62 and the rate of apoptotic cells elevated [p62 ( A value): 3.50±0.47 vs. 1.51±0.32, apoptotic cells rate: (44.53±10.15)% vs. (23.03±1.91)%, both P < 0.05]. Conclusion:Bradykinin postconditioning played a neuroprotective role in CPR rats by activating autophagy and reducing apoptosis.

Mesenchymal stem cells transplantation improves functional recovery after cardiac arrest: contribution of necroptosis / 中华急诊医学杂志

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.

Evaluation and Experience of Clinical Effect of Minimally Invasive Drainage and Craniotomy in the Treatment of Patients with Epidural Hematoma / 现代生物医学进展

Objective:To analyse the evaluation and experience of clinical effect of minimally invasive drainage and craniotomy in the treatment of patient with epidural hematoa.Methods:100 cases of patients who were diagnosed as epidural hematoma from January 2015 to January 2016 were selected and randomly divided into two groups,where the control group were given craniotomy,and the observation group were given minimal invasive drainage.The effect of the surgery and the life qualities before and after treatment of the two groups were compared.Results:The effect of observation group is better than that of control group (P ＜ 0.05);craniocerebral defect and the re-hemorrhage incidence occurrence in the observation group were obviously lower than those in the control group,(0 ％,6 ％ vs 12 ％,20 ％) (P＜0.05).Conclusion:Compared with craniotomy,minimal invasive drainage in clinical treatment of epidural hematoma showed advantage in at smaller trauma,faster recovery,and better effect,thus deserving further promotion of clinic application.

Prognostic value of first documented rhythms in patients with in-hospital cardiac arrest / 中华急诊医学杂志

Objective To evaluate the prognostic value of the first documented rhythm in patients with in-hospital cardiac arrest.Methods The clinical data of 62 in-hospital cardiac arrest patients collected from May 2011 to April 2016 were reviewed.Multiple regression analysis was performed for determination of the factors relevant to ROSC.The patients were divided into defibrillative rhythm group [ventricular fibrillation (VF) /ventricular tachycardia (VT)] and non-defibrillative rhythm group [pulseless electrical activity (PEA) /asystole] according to the first documented rhythm after cardiac arrest.The differences in rate of restoration of spontaneous circulation,number of survival at hospital discharge and those discharged with favorable neurological outcome were compared between groups.Results Logistic regression analysis showed that non-defibrillative rhythm was related to low rate of ROSC.Rate of ROSC (x2 =6.90,P =0.01),number of survival at hospital discharge (x2 =10.49,P =0.00) and those discharged with favorable neurological outcome (x2 =14.70,P =0.00) were higher in the defibrillative rhythm group,while there was no difference in outcomes between the VF and VT groups.There was no difference in consequence found between the PEA and asystole groups.Conclusion Rate of restoration of spontaneous circulation,number of survival at hospital discharge and those discharged with favorable neurological consequence were higher with defibrillative initial rhythm.

Diffusion tensor imaging of brain white matter in rats with ischemia reperfusion injury and its behavioral changes / 中华急诊医学杂志

Objective To investigate the changes of diffusion tensor imaging (DTI) in the cerebral white matter of rats with ischemia-reperfusion injury.Methods Adult SD rats were randomly divided into two groups,sham operation group and model group.The model of ischemia reperfusion injury was made by the Koizumi suture method to occlude the middle cerebral artery.Application of Zea-Longa score was carried out to determine the establishment of modeling,and the modified neurological severity score (mNSS) was used to evaluate the neurological deficit of rats.The Rotarod test instrument was used to observe the motor function of rats by using Rotarod fatigue balance signs,and the DTI sequence scanning observation of brain white matter nerve fiber damage was determined by using Brook 7.0T small animal magnetic resonance imaging system.Track Vis software was used to analyze the distribution of cerebral white matter nerve fibers,and the relative number of nerve fibers in the areas of ROI (region of interest,ROI),sensorimotor areas and striatum were calculated.Results The results showed varying degrees of neurological impairment in rats 2 h after cerebral ischemia reperfusion injury,and the Zea-Longa score and the mNSS score were gradually reduced at the 1 d,7 d and 14 d after ischemia reperfusion injury.The time of rats retaining on the rotating rod was shortened at the 7 d and 14 d after ischemia reperfusion injury.At the ischemic lateral,nerve fibers decreased significantly,and the number of sensory nerve fiber connections in the sensorimotor areas to striatum was reduced.Nissl staining showed that the cytoplasm of neurons in the sensorimotor cortex and striatum of the ischemic lateral were disappeared and the Nissl bodies were decreased.Conclusions The nerve fibers of sensory motor cortex connecting to striatum were damaged by ischemia reperfusion injury.

Suppression of inflammatory damage to the brain after global cerebral ischemia by transplanted mesenchymal stem cells via secretion of TSG-6

Objective: Numerous studies have shown that bone marrow-derived mesenchymal stem cells (MSCs) enhance neurological recovery after cerebral ischemia. However, the mechanisms are still not clear. The present study aimed to investigate the beneficial effects of MSCs on global cerebral ischemia induced by cardiac arrest (CA) and the underlying mechanisms. Methods: Rats subjected to asphyxial CA were injected intravenously with MSCs (5×106 ) at 2 hours after resuscitation. Whole brain histopathologic damage scores (HDS) were assessed by histopathology at 3 and 7 days after resuscitation. The distribution of donor MSCs in the brain was evaluated. The expression of tumor necrosis factor-α-induced protein 6 (TSG-6) and pro-inflammatory cytokines in cerebral cortex was assayed. After intravenous infusion of TSG-6 siRNA-MSCs, HDS and pro-inflammatory cytokines were reevaluated at 7 days after resuscitation. Results: Intravenously administered MSCs significantly reduced whole brain HDS after global cerebral ischemia. Immunofluorescence microscopy revealed that donor MSCs were primarily found in cerebral cortex and expressed TSG-6. MSCs treatment significantly increased the expression of TSG-6 and reduced the expression of pro-inflammatory cytokines in cerebral cortex. In addition, intravenous infusion of TSG-6 siRNA-MSCs failed to attenuate brain inflammation. Conclusion: Systemically administered MSCs reduced inflammatory damage to brain in rats with global cerebral ischemia via secretion of TSG-6.

Changes and clinical significance of ischemia modified albumin in patients with cardiopulmonary resuscitation / 中华急诊医学杂志

Objective To study the changes in the level of serum IMA in patients with cardiac arrest followed by CPR,and explore the value of serum IMA in predicting prognosis of these patients after CPR.Methods (1) A total of 36 patients (25 men and 11 women) after CPR following cardiac arrest were recruited into experimental group (group C).Of them,15 cases (11 men and 4 women) and 21 cases (14men and 7 women) were assigned into resuscitation group (group R) and non resuscitation group (group NR),respectively,according to the presence or absence of ROSC.Meanwhile,another 60 healthy subjects (39 men and 21 women) matched for age and gender were recruited into healthy control group (group H).(2) The determination of the serum IMA level and comparisons of changes in serum IMA levels among groups were carried out.Results (1) The level of serum IMA in group C was higher than that in group H (P ＜ 0.05) ; The serum IMA level in group R was lower than that in group NR and higher than that in group H (P ＜0.05 for both).(2) The area under the ROC curve for serum IMA in predicting the prognosis of patients treated with CPR after cardiac arrest was 0.73.When the cut off value was 128.25 U/mL,the sensitivity and specificity were 57.1％ and 93.3％ respectively; the positive predictive value and negative predictive value were 92.3％ and 60.9％ ; positive likelihood ratio and negative likelihood ratio were 8.5 and 0.5 ; the correct diagnosis index was 72.2％,and Youden index was 50.5％.Conclusions Serum IMA has a certain value in prediction of prognosis in patients treated with CPR following cardiac arrest.

The efficacy of mild hypothermia for the treatment of patients successfully resuscitated from cardiac arrest: a meta-analysis / 中华急诊医学杂志

Objective To study the effectiveness and safety of therapeutic mild hypothermia in patients successfully resuscitated from cardiac arrest using a meta-analysis.Methods We searched the MEDLINE (1966-April 2012),OVID (1980 to April 2012),EMBASE (1980 to April 2012),Chinese bio-medical literature & retrieval system (CBM) (1978 to April 2012),Chinese medical current contents (CMCC) (1995 to April 2012),and Chinese medical academic conference (CMAC) (1994 to April 2012).Studies were included (1) the study design was a randomized controlled trial (RCT); (2) the study population included patients successfully resuscitated from cardiac arrest,and received either conventional post-resuscitation care with normothermia or mild hypothermia; (3) the study provided data about good neurologic outcome and survival till hospital discharge.Relative risk (RR) and 95％ corfidence interval (CI) were used to pool the effect.Results The study included four RCTs with a collected total of 417 patients successfully resuscitated from cardiac arrest.Compared to conventional post-resuscitation care with normothermia,patients in the hypothermia group were more likely to have good neurologic outcome (RR =1.43,95％ CI 1.14 ～ 1.80,P =0.002) and were more likely to survive till hospital discharge (RR =1.32,95％ CI 1.08 ～ 1.63,P =0.008).From all over the studies there was no significant difference in reported adverse events between the normothermia and hypothermia group (P ＞ 0.05).There did not exist heterogeneity and publication bias.Conclusions Therapeutic mild hypothermia improves neurologic outcome and survival in patients successfully resuscitated from cardiac arrest.