Manlin Duan

The Effect of Hydrogen-Rich Saline on the Brain of Rats with Transient Ischemia

BACKGROUND Due to its antioxidant and anti-inflammatory properties, hydrogen gas (H(2)) has protective effects on a variety of organs from damage induced by ischemia/reperfusion (I/R). In this study, we tested the protective effect of hydrogen-rich saline on the brain in a global cerebral I/R model. MATERIALS AND METHODS We used a four-vessel occlusion model of global cerebral ischemia (15 min) and reperfusion with rats. The rats were divided into four groups (n = 96): sham, I/R plus physiologic saline injected intraperitoneally, I/R plus hydrogen-rich saline injected intraperitoneally at the beginning of reperfusion, and I/R plus hydrogen-rich saline injected intraperitoneally 6 h after reperfusion began. One group of rats was sacrificed after 24 h of reperfusion. Malondialdehyde (MDA) was measured to quantify the oxidative stress. Caspase-3 was measured to indicate the status of apoptosis. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-κB (NF-κB) were measured to monitor the inflammation. Another group of rats was sacrificed after 72 h of reperfusion to measure the histologic damages in hippocampus by hematoxylin and eosin staining and Nissl staining. RESULTS Compared with rats with I/R only, hydrogen-rich saline treatment significantly improved the amount of surviving cells. NF-κB, TNF-α, IL-6, MDA, and caspase-3 were all increased significantly by I/R injury. Hydrogen-rich saline reduced all these markers. CONCLUSIONS Our data demonstrate that intraperitoneal injection of hydrogen-rich saline has strong protective effect on the transient global cerebral ischemia-reperfusion rats.

Therapeutic hypothermia attenuates global cerebral reperfusion-induced mitochondrial damage by suppressing dynamin-related protein 1 activation and mitochondria-mediated apoptosis in a cardiac arrest rat model

Therapeutic hypothermia is effective to attenuate brain ischemia/reperfusion (I/R) injury after cardiac arrest, and multiple mechanisms have been proposed. Dynamin-related protein 1 (Drp1), a large GTPases of dynamin superfamily, predominantly controls mitochondrial fission and is related to IR-induced Cyt C release and apoptosis. However, the effect of therapeutic hypothermia on Drp1 and mitochondrial fission after cardiac arrest remains still unclear. In this study, non-cardiac arrest and post-cardiac arrest rats received 6-h normothermia (37-38°C) or therapeutic hypothermia (32-34°C), and the hippocampus was harvested at 6h and 72h after cardiac arrest. Results showed the expression of Drp1 and Cyt C increased after cardiac arrest, but therapeutic hypothermia partially reversed this increase at 6h after cardiac arrest. Transmission electron microscopy (TEM) also showed a change in morphology following therapeutic hypothermia after cardiac arrest. Moreover, therapeutic hypothermia could decrease the histopathological damage, inhibit the apoptosis of CA1 neurons and improve the survival and neurological outcomes at 72h after cardiac arrest. Taken together, our study demonstrates that therapeutic hypothermia is neuroprotective against global cerebral I/R injury, which is, at least partially, ascribed to the inhibition Drp1 and Cyt C expression and the protection of mitochondrial structure.

Efficacy of Mild Hypothermia for the Treatment of Patients with Cardiac Arrest

Background:Therapeutic hypothermia has been recommended for the treatment of cardiac arrest patients who remain comatose after the return of spontaneous circulation. The aim of this study was to evaluate the effectiveness and safety of mild hypothermia on patients with cardiac arrest by conducting a meta-analysis. Methods:The relevant trials were searched in Cochrane Library, PubMed, Web of Science, Embase, CNKI and Wan Fang Data from the date of their establishment to October 2014. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted, and the quality of the included studies was evaluated. A meta-analysis was conducted using the Cochrane Collaboration Review Manager 5.2 software. Results:Six randomized controlled trials involving 531 cases were included, among which 273 cases were assigned to the treatment group and the other 258 cases to the control group. The meta-analysis indicated that mild hypothermia therapy after cardiac arrest produced significant differences in survival rate (relative risk [RR] =1.23, 95% confidence interval [CI]: 1.02–1.48, P = 0.03) and neurological function (RR = 1.33, 95% CI: 1.08–1.65, P = 0.007) after 6 months compared with normothermia therapy. However, no significant differences were observed in the survival to the hospital discharge (RR = 1.35, 95% CI: 0.87–2.10, P = 0.18), favorable neurological outcome at hospital discharge (RR = 1.53, 95% CI: 0.95–2.45, P = 0.08) and adverse events. Conclusions:The meta-analysis demonstrated that mild hypothermia can improve the survival rate and neurological function of patients with cardiac arrest after 6 months. On the other hand, regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and adverse events, our meta-analysis produced nonsignificant results.

Hydrogen-rich saline attenuates hippocampus endoplasmic reticulum stress after cardiac arrest in rats.

BACKGROUND Hydrogen-rich saline can selectively scavenge reactive oxygen species (ROS) and protect brain against ischemia reperfusion (I/R) injury. Endoplasmic reticulum stress (ERS) has been implicated in the pathological process of cerebral ischemia. However, very little is known about the role of hydrogen-rich saline in mediating pathophysiological reactions to ERS after I/R injury caused by cardiac arrest. METHODS The rats were randomly divided into three groups, sham group (n=30), ischemia/reperfusion group (n=40) and hydrogen-rich saline group (n=40). The rats in experimental groups were subjected to 4min of cardiac arrest and followed by resuscitation. Then they were randomized to receive 5ml/kg of either hydrogen-rich saline or normal saline. RESULTS Hydrogen-rich saline significantly improves survival rate and neurological function. The beneficial effects of hydrogen-rich saline were associated with decreased levels of oxidative products, as well as the increased levels of antioxidant enzymes. Furthermore, the protective effects of hydrogen-rich saline were accompanied by the increased activity of glucose-regulated protein 78 (GRP78), the decreased activity of cysteinyl aspartate specific proteinase-12 (caspase-12) and C/EBP homologous protein (CHOP). CONCLUSIONS Hydrogen-rich saline attenuates brain I/R injury may through inhibiting hippocampus ERS after cardiac arrest in rats.