Granulocyte-colony stimulating factor for stroke treatment: mechanisms of action and efficacy in preclinical studies

G-CSF is widely employed for the treatment of chemotherapy-induced neutropenia. Recently, neuroprotective effects of G-CSF in animal stroke models were discovered including infarct size reduction and enhancement of functional recovery. The underlying mechanisms of action of G-CSF in ischemia appear to be a direct anti-apoptotic activity in neurons and a neurogenesis inducing capacity. Additional effects may be based on the stimulation of new blood-vessel formation, the stimulation of immunocompetence and -modulation as well as on bone marrow mobilization. In addition to a discussion of these mechanisms, we will review the available preclinical studies and analyze their impact on the overall efficacy of G-CSF in experimental stroke

Sodium-Dependent Vitamin C Transporter 2 (SVCT2) Expression and Activity in Brain Capillary Endothelial Cells after Transient Ischemia in Mice

Expression and transport activity of Sodium-dependent Vitamin C Transporter 2 (SVCT2) was shown in various tissues and organs. Vitamin C was shown to be cerebroprotective in several animal models of stroke. Data on expression, localization and transport activity of SVCT2 after cerebral ischemia, however, has been scarce so far. Thus, we studied the expression of SVCT2 after middle cerebral artery occlusion (MCAO) in mice by immunohistochemistry. We found an upregulation of SVCT2 after stroke. Co-stainings with Occludin, Von-Willebrand Factor and CD34 demonstrated localization of SVCT2 in brain capillary endothelial cells in the ischemic area after stroke. Time-course analyses of SVCT2 expression by immunohistochemistry and western blots showed upregulation in the subacute phase of 2–5 days. Radioactive uptake assays using 14C-labelled ascorbic acid showed a significant increase of ascorbic acid uptake into the brain after stroke. Taken together, these results provide evidence for the expression and transport activity of SVCT2 in brain capillary endothelial cells after transient ischemia in mice. These results may lead to the development of novel neuroprotective strategies in stroke therapy

Granulocyte-Colony Stimulating Factor (G-CSF) in Stroke Patients with Concomitant Vascular Disease—A Randomized Controlled Trial

G-CSF has been shown in animal models of stroke to promote functional and structural regeneration of the central nervous system. It thus might present a therapy to promote recovery in the chronic stage after stroke.Here, we assessed the safety and tolerability of G-CSF in chronic stroke patients with concomitant vascular disease, and explored efficacy data. 41 patients were studied in a double-blind, randomized approach to either receive 10 days of G-CSF (10 µg/kg body weight/day), or placebo. Main inclusion criteria were an ischemic infarct >4 months prior to inclusion, and white matter hyperintensities on MRI. Primary endpoint was number of adverse events. We also explored changes in hand motor function for activities of daily living, motor and verbal learning, and finger tapping speed, over the course of the study.Adverse events (AEs) were more frequent in the G-CSF group, but were generally graded mild or moderate and from the known side-effect spectrum of G-CSF. Leukocyte count rose after day 2 of G-CSF dosing, reached a maximum on day 8 (mean 42/nl), and returned to baseline 1 week after treatment cessation. No significant effect of treatment was detected for the primary efficacy endpoint, the test of hand motor function.These results demonstrate the feasibility, safety and reasonable tolerability of subcutaneous G-CSF in chronic stroke patients. This study thus provides the basis to explore the efficacy of G-CSF in improving chronic stroke-related deficits.ClinicalTrials.gov NCT00298597

Impact of pulmonary embolism on acute chronic obstructive pulmonary disease exacerbation

© Copyright 2017 by Gazi University Medical Faculty-Available on-line at web site http://medicaljournal.gazi.edu.tr/.Purpose: This study aims to assess effect of pulmonary embolism (PE) on clinical and laboratory parameters of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Risk factors for PE development were also evaluated. Methods: In this retrospective study, patients who were hospitalized for AECOPD and underwent computed tomographic pulmonary angiography scan (CTPA) between 2009 and 2011 were included. Patients with PE were evaluated separately as those diagnosed at initial examination and those suspected during exacerbation therapy since they had inadequate response. Binary logistic regression analysis was used in order to determine risk factors on PE development. Results: The study consisted of 36 patients, 13 patients (36.1%) had PE. FEV1 and FEV1/FVC values were higher in PE group (53.7% vs 41.4%; 62.3% vs 52% respectively; p<0.05). There was no difference between D-dimer levels of PE and non-PE patients. Risk of PE development did not differ with analyzed variables. Those-diagnosed at initial examination had significantly less number of exacerbations in the last one year than those diagnosed during therapy (1.1 vs 3.2; p<0.05). Conclusion: PE should always be considered in AECOPD etiology, particularly in patients with frequent exacerbation history and D-dimer levels may be misleading

Protective effects of safranal against subchronic thinner inhalation induced oxidative stress in rats

339-348In phytotherapy, research on the effects of components in plant extracts on various diseases gets increasing attention. . Saffron is an herb with antioxidant effects, known to have an increasing significance due to its therapeutic effects. Safranal is one of the components of saffron extract. Here, we explored the effects of subchronic thinner inhalation on the oxidant-antioxidant balance, the relation between toxicity and oxidative stress, and a possible protective effect of safranal against thinner toxication in rats. Sprague−Dawley rats were divided into four groups as follows: control (Gr. I), safranal (Gr. II), thinner (Gr. III) and thinner+safranal Gr. IV). Each group consisted of 10 rats, and the study lasted for 8 weeks. After completing the animal studies malondialdehyde (MDA), reduced glutathione (GSH), toluol, 8OHdG (8-hydroxy-2-deoxyguanosine), protein oxidation, nitric oxide metabolites (NOx), total antioxidant capacity (TAC), total oxidant capacity (TOC), glucose, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, WBC, VLDL, RBC, HCT, Hb, aspartate amino transferase (AST), and alanine amino transferase (ALT) levels were determined from blood specimens of the rats. Brain and lung tissues were also examined histopathologically. The data obtained from the study were statistically analyzed using SPSS, and both ANCOVA and Bonferroni tests were performed. P <0.05 was accepted as statistically significant. The results indicated that safranal had a protective and balancing effect against thinner inhalation oriented complications in rats