We investigated the potential benefit of using a local infusion of low-dose and cold human albumin in ischemic rats as compared with systemic delivery.
Stroke was induced in rats, and at 2 hours ...treatment groups received 0°C saline or low-dose albumin at 0°C or 37°C infused into the ischemic area.
The local low-dose cold albumin infusion, which achieved the hypothermic temperature (P<0.001), produced the greatest reduction in infarct volume and the best recovery of neurological function.
The local low-dose cold albumin infusion into the ischemic area offered a combination of regional brain hypothermia and albumin administration, which enhanced neuroprotection and would be beneficial in the clinical setting.
Treatment of adipose-derived stem cell (ADSC) substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting ...neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E) may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO). We demonstrated that intravenous (IV) injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.
Spontaneous intracerebral hemorrhage (ICH) accounts for 10–20% of all strokes and contributes to higher mortalities and severe disabilities. The aims of this study were, therefore, to characterize ...novel biomarkers, metabolic disruptions, and mechanisms involving ICH. A total 30 ICH patients and 30 controls were enrolled in the study, and their clinical characteristics were analyzed. Nontargeted metabolomic analysis was conducted using ultra‐performance liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry (UPLC/Q‐TOF). Multivariate statistical analysis and receiver operating characteristic curve analysis were used for screening and evaluating the predictive ability of biomarkers. ICH patients showed significantly higher systolic blood pressure, diastolic blood pressure, blood glucose levels, white blood cell counts, neutrophil count, percentage of neutrophils and globulin and a lower albumin/globin ratio when compared with controls. In sum, 11 important metabolites were identified, which were associated with disruption of fatty acid oxidation and sphingolipid and phospholipid metabolism, as well as increased inflammation, oxidative stress, and vascular pathologies. Further multiple logistic regression analyses of these metabolites showed that l‐carnitine and phosphatidylcholine (20:3/22:6) have potential as biomarkers of ICH, and the area under the curve, sensitivity, specificity were 0.974, 90%, and 93%, respectively. These findings provide insights into the pathogenesis, early prevention, and diagnosis of ICH.
Mitochondria is a double membrane‐bound cellular organelle that generates energy to maintain the homeostasis of cells. Immunity‐related GTPase M (IRGM) in human locates at the inner membrane of ...mitochondria and is best known for its role in regulating autophagy against intracellular pathogens. Previous studies have shown that IRGM is crucial for the normal function of mitochondria, yet, the molecular mechanisms underlying IRGM‐mediated quality control of mitochondria are still not fully understood. In this study, we showed that knocking‐down IRGM inhibits CCCP induced mitophagy in SH‐SY5Y cells. Furthermore, we reported that IRGM decreases the stability of Mitofilin (IMMT, MIC60) in the damaged mitochondria. Knocking down Mitofilin rescues the loss of mitophagy that is observed in the IRGM KD cells, suggesting that IRGM regulates mitophagy through the inhibition of Mitofilin. These data together provide molecular insight regarding how IRGM regulates mitophagy to control the quality of mitochondria.
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Over decades, nearly all attempts to translate the benefits of therapeutic hypothermia in stroke models of lower-order species to stroke patients have failed. Potentially overlooked ...reasons may be biological gaps between different species and the mismatched initiation of therapeutic hypothermia in translational studies. Here, we introduce a novel strategy of selective therapeutic hypothermia in a non-human primate ischemia-reperfusion model, in which autologous blood was cooled ex vivo and the cool blood transfusion was administered at the middle cerebral artery just after the onset of reperfusion. Cold autologous blood cooled the targeted brain rapidly to below 34 °C while the rectal temperature remained around 36 °C with the assistance of a heat blanket during a 2-h hypothermic process. Therapeutic hypothermia or extracorporeal-circulation related complications were not observed. Cold autologous blood treatment reduced infarct sizes, preserved white matter integrity, and improved functional outcomes. Together, our results suggest that therapeutic hypothermia, induced by cold autologous blood transfusion, was achieved in a feasible, swift, and safe way in a non-human primate model of stroke. More importantly, this novel hypothermic approach conferred neuroprotection in a clinically relevant model of ischemic stroke due to reduced brain damage and improved neurofunction. This study reveals an underappreciated potential for this novel hypothermic modality for acute ischemic stroke in the era of effective reperfusion.
Highlights • 1 GeneChip was used to screen the differentially expressed miRNAs. • 2 RT-qPCR was used to verify the results of microarray. • 3 ROC curve was performed to evaluate the sensitivity and ...specificity. • 4 miR-129-2-3p was upregulated in patients with refractory epilepsy. • 5 Plasma miR-129-2-3p has great potential as a clinically useful biomarker.
Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some ...distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence‐based Medicine Center of Lanzhou University, was established to develop evidence‐based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta‐analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients’ preferences. Finally, 20 recommendations were developed through the Delphi‐based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.
The aim of the present study was to investigate the effects of surgical intervention of focal cortical dysplasia (FCD) IIa on the outcome of epilepsy, and to evaluate the prognostic factors of ...seizure freedom. Patient data from epilepsy surgeries were retrospectively reviewed at the Second Affiliated Hospital of Dalian Medical University between 2007 and 2015. A total of 110 patients with a definite pathological diagnosis of FCD IIa were included. Moreover, the clinical characteristics, seizure outcome and quality of life in adults with FCD IIa were evaluated. The Engel seizure outcome achievements were class I in 72, class II in 20, class III in 11 and class IV in 7 patients. In addition, the Engel seizure outcome was relevant with the resection range of the lesions (P=0.028). The assessments of electrocorticography (ECoG) patterns and magnetic resonance imaging (MRI) are relevant to determining the extent of the resection, which may influence the surgery outcome (P=0.001 and P=0.023). Using multivariate regression analyses, the extent of resection, seizure frequency, preoperative ECoG and location of resection were the most important risk factors for seizure recurrence. The results of quality of life in epilepsy-10 scoring revealed that the quality of life improved significantly following surgery (P<0.01). Moreover, surgical intervention, EcoG, MRI positioning and complete resection helped to have improved seizure control, relief of anxiety and quality of life. All these observations strongly recommend an early consideration of epilepsy surgery in FCD IIa patients.
Objective: The neuroprotective effect of hypothermia has been well established. The use of hypothermia for the treatment of stroke by systemic hypothermia is limited by the cooling rate and has ...severe complications. The goal of this study was to determine if local cerebral cooling via infusion could reduce infarction volume and improve the neurological outcome in a rat model of middle cerebral artery (MCA) occlusion.
Methods: A hollow filament was used to block the MCA for 2 hours, and then the ischemic territory was locally infused with autocirculating cold arterial blood (13-15°C). This cold blood infusion (<0.6 ml/min) significantly reduced the temperature of the MCA supplied territory to 32-34°C in 5-10 minutes. This hypothermic procedure was maintained for 30 minutes. After evaluating the neurological score at 2 days and 28 days, all animals were euthanized and their brains were sectioned and stained with hematoxylin and eosin (H&E). Their infarct volumes were calculated.
Results: Local mild hypothermia in the brain was induced by autocirculation with a cold blood infusion, whereas the rectal temperature was maintained within the normal range. The infarction volume was significantly reduced and the neurological outcome was significantly improved (p<0.05) after MCA occlusion in Group 2 (hypothermia) compared with Group 1 (MCA occlusion) and Group 3 (normothermia).
Conclusion: Local brain hypothermia induced by autocirculating cold arterial blood infused into ischemic tissue has neuroprotective effects.
Summary Interventional management of acute stroke can significantly increase recanalization rate of the occluded artery, however, this improvement is achieved at the expense of an increased incidence ...in symptomatic intracranial hemorrhage, which may markedly reduce the therapeutic benefit of this treatment. Hypothermia is one of the most promising neuroprotective approaches studied. It may also lower the risk of postischemic hemorrhage by reducing the activities of matrix metalloproteinases and blood-brain barrier disruption. But in most clinical studies, hypothermia is induced by surface cooling. It has two major drawbacks. (1) Several hours are required to reach the target body core temperature. (2) The incidence of adverse effects, such as impaired immune function, shivering, pneumonia, and cardiac arrhythmias/bradycardias, is high. Selective brain hypothermia without reducing body core temperature can theoretically address both problems of whole body cooling. So it is hypothesized that interventional management of acute stroke combined with catheter-based selective brain hypothermia may reduce the risk of postischemic hemorrhagic transformation, at the same time circumventing the bulk of negative side effects associated with systemic hypothermia.
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