Hydrogen-rich saline alleviates early brain injury through inhibition of necroptosis and neuroinflammation via the ROS/HO-1 signaling pathway after traumatic brain injury.

Traumatic brain injury (TBI) has been recognized as a serious public health issue and a key contributor to disability and death, with a huge economic burden worldwide. Hydrogen, which is a slight and specific cytotoxic oxygen radical scavenger, has been demonstrated to ameliorate early brain injury (EBI) through reactive oxygen species (ROS), oxidative stress injury, apoptosis and necroptosis. Necroptosis refers to a type of programmed cell death process that has a vital function in neuronal cell death following TBI. The specific function of necroptosis in hydrogen-mediated neuroprotection after TBI, however, has yet to be determined. The present study aimed to examine the neuroprotective effects and possible molecular basis that underly hydrogen-rich saline in TBI-stimulated EBI by examining neural necroptosis in the C57BL/6 mouse model. The brain water content, neurological score, neuroinflammatory cytokines (NF-κΒ, TNF-α, IL-6 and IL-1ß) and ROS were evaluated using flow cytometry. Malondialdehyde, superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated using a biochemical kit. Receptor-interacting protein kinase (RIP)1, RIP3, Nrf2 and Heme oxygenase-1 (HO-1) were evaluated using western blotting. mRNA of Nrf2 and HO-1 were evaluated using quantitative PCR. Neuronal death was evaluated by TUNEL staining. The outcomes illustrated that hydrogen-rich saline treatment considerably enhanced the neurological score, increased neuronal survival, decreased the levels of serum MDA and brain ROS, increased the levels of serum GSH and SOD. In addition the protein expression levels of RIP1 and RIP3 and the cytokines NF-κB, TNF-α, IL-1ß and IL-6 were downregulated compared with the TBI group, which demonstrated that hydrogen-rich saline-induced inhibition of necroptosis and neuroinflammation ameliorated neuronal death following TBI. The neuroprotective capacity of hydrogen-rich saline was demonstrated to be partly dependent on the ROS/heme oxygenase-1 signaling pathway. Taken together, the findings of the present study indicated that hydrogen-rich saline enhanced neurological outcomes in mice and minimized neuronal death by inducing protective effects against neural necroptosis as well as neuroinflammation.

The neuroprotection of cerebrolysin after spontaneous intracerebral hemorrhage through regulates necroptosis via Akt/ GSK3ß signaling pathway.

PURPOSE: Spontaneous intracerebral hemorrhage (ICH) is a major cause of death and disability with a huge economic burden worldwide. Cerebrolysin (CBL) has been previously used as a nootropic drug. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the precise role of necroptosis in CBL neuroprotection following ICH has not been confirmed. METHODS: In the present study, we aimed to investigate the neuroprotective effects and potential molecular mechanisms of CBL in ICH-induced early brain injury (EBI) by regulating neural necroptosis in the C57BL/6 mice model. Mortality, neurological score, brain water content, and neuronal death were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Evans blue extravasation, Western blotting, and quantitative real-time polymerase chain reaction (PCR). RESULTS: The results show that CBL treatment markedly increased the survival rate, neurological score, and neuron survival, and downregulated the protein expression of RIP1 and RIP3, which indicated that CBL-mediated inhibition of necroptosis, and ameliorated neuronal death after ICH. The neuroprotective capacity of CBL is partly dependent on the Akt/GSK3ß signaling pathway. CONCLUSIONS: CBL improves neurological outcomes in mice and reduces neuronal death by protecting against neural necroptosis.

The neuroprotection of cerebrolysin after spontaneous intracerebral hemorrhage through regulates necroptosis via Akt/ GSK3B signaling pathway

ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major cause of death and disability with a huge economic burden worldwide. Cerebrolysin (CBL) has been previously used as a nootropic drug. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the precise role of necroptosis in CBL neuroprotection following ICH has not been confirmed. Methods: In the present study, we aimed to investigate the neuroprotective effects and potential molecular mechanisms of CBL in ICH-induced early brain injury (EBI) by regulating neural necroptosis in the C57BL/6 mice model. Mortality, neurological score, brain water content, and neuronal death were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Evans blue extravasation, Western blotting, and quantitative real-time polymerase chain reaction (PCR). Results: The results show that CBL treatment markedly increased the survival rate, neurological score, and neuron survival, and downregulated the protein expression of RIP1 and RIP3, which indicated that CBL-mediated inhibition of necroptosis, and ameliorated neuronal death after ICH. The neuroprotective capacity of CBL is partly dependent on the Akt/GSK3β signaling pathway. Conclusions: CBL improves neurological outcomes in mice and reduces neuronal death by protecting against neural necroptosis.

Botulinum Toxin Type A for Upper Limb Spasticity in Poststroke Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Botulinum toxin type A is considered to be an effective antispasmodic in recent years. We assess the effectiveness of botulinum toxin type A for the treatment of poststroke spasticity in the upper extremity using a meta-analysis. METHODS: We searched several databases including PubMed, Web of Science, Embase, and Cochrane database for relevant studies, up until October 2017. All randomized controlled trials of botulinum toxin type A treat poststroke upper limb spasticity published were included. The primary outcome measure was modified ashworth score at the elbow, finger and wrist, pain score, and barthel index. RESULTS: Ten randomized controlled trials were identified and reported sufficient data for inclusion in the pooled analysis (n = 950). The results of modified ashworth score at different joints, pain score, barthel index showed no difference was found in the effectiveness of botulinum toxin type A compared with placebo in the treatment of the upper limb spasticity after stroke. But modified ashworth score at the elbow was improver in Dysport subgroups (standardized mean difference [SMD] = -.39, 95%CI = -.67 to -.10, P = .008) compared with Botox subgroups (SMD = .08, 95%CI = -.68 to .83, P = .84). CONCLUSIONS: The meta-analysis of these studies showed that the overall effectiveness of botulinum toxin type A does not seem to differ from placebo for poststroke Patients. But the meta-analysis yielded a favorable effect of Dysport compared with placebo based on 4 trials.

Efficacy and feasibility of antidepressant treatment in patients with post-stroke depression.

BACKGROUND: Depression greatly impacts the quality of life in most stroke survivors. Therefore, effective treatment of post-stroke depression (PSD) is critically important. However, evidence supporting the effectiveness and feasibility of antidepressant treatment in this population is limited and somewhat confusing. METHODS: A comprehensive literature search of the Cochrane, PubMed, Web of Science, and Embase databases from inception up to November 2015 was conducted. We reviewed all randomized controlled trials (RCTs) that assigned patients with a clinical diagnosis of PSD to antidepressant or placebo treatment. Reduction in depression rating scale scores and response rate to antidepressants were defined as the efficacy outcomes. Rates of dropout for any reason and for adverse effects were defined as the acceptability outcomes. We also assessed improvements in activities of daily living (ADL) as functional outcomes. RESULTS: In total, 11 trials consisting of 740 participants were indentified. A significant advantage of antidepressants compared with placebo treatment in PSD was observed in overall pooled effect size analysis (SMD = -0.96; 95% CI = -1.41 to -0.51; P <0.0001). In addition, patients receiving antidepressants presented a much greater improvement in various depressive symptoms than those with placebo (RR = 1.36; 95% CI = 1.01-1.83; P = 0.04). However, antidepressants were less well tolerated than placebo because of some adverse events (RR = 2.72; 95% CI = 1.37-5.43; P = 0.04). Intriguingly, no consistent evidence was found for a positive effect of antidepressants on ADL in our analysis. CONCLUSIONS: This meta-analysis suggests that antidepressants treatment confers potentially positive effects in patients with PSD as compared with simple placebo treatment. However, this must be carefully considered in light of its possible adverse events in some individual patients.