Protection of hippocampal CA1 neurons against ischemia/reper-fusion injury by exercise preconditioning via modulation of Bax/ Bcl-2 ratio and prevention of caspase-3 activation

Introduction: Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia

Methods: Male rats weighing 260-300 g were randomly allocated into three groups [sham, exercise, and ischemia]. The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries [CCAs] for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining

Results: The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group [P<0.001], and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group [P<0.05]. Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group [P<0.001]

Discussion: This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli

Magnetic resonance imaging of human-derived amniotic membrane stem cells using PEGylated superparamagnetic iron oxide nanoparticles

Objective: the label and detection of cells injected into target tissues is an area of focus for researchers. Iron oxide nanoparticles can be used to label cells as they have special characteristics. The purpose of this study is to examine the effects of iron oxide nanoparticles on human-derived amniotic membrane stem cell [hAMCs] survival and to investigate the magnetic properties of these nanoparticles with increased contrast in magnetic reso-nance imaging [MRI]

Materials and Methods: in this experimental study, we initially isolated mesenchymal stem cells from amniotic membranes and analyzed them by flow cytometry. In addition, we synthesized superparamagnetic iron oxide nanoparticles [SPIONs] and characterized them by various methods. The SPIONs were incubated with hAMCs at concentrations of 25-800 [micro]g/mL. The cytotoxicity of nanoparticles on hAMCs was measured by the MTT assay. Next, we evaluated the effectiveness of the magnetic nanoparticles as MRI contrast agents. Solutions of SPION were prepared in water at different iron concentrations for relaxivity measurements by a 1.5 Tesla clinical MRI instrument

Results: the isolated cells showed an adherent spindle shaped morphology. Polyethylene glycol [PEG]-coated SPIONs exhibited a spherical morphology. The average particle size was 20 nm and magnetic saturation was 60 emu/g. Data analysis showed no significant reduction in the percentage of viable cells [97.86 +/- 0.41%] after 72 hours at the 125 [micro]g/ml concentration compared with the control. The relaxometry results of this SPION showed a transverse relaxivity of 6.966 [[micro]g/ml.s][-1]

Conclusion: SPIONs coated with PEG used in this study at suitable concentrations had excellent labeling efficiency and biocompatibility for hAMCs

Improvement of heart failure by human amniotic mesenchymal stromal cell transplantation in rats

Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells [hAMSCs] in rats with heart failure [HF]

Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups [7 rats each] as 1- Control 2- Heart Failure [HF] 3- Sham 4- Culture media 5- Stem Cell Transplantation [SCT]. Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×106 cells in 150 microl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done

Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 +/- 9% to 81/25 +/- 6/05% in SCT group [p value < 0.001]. Fraction shortening in HF group was increased from 27/53 +/- 8/58% into 45/55 +/- 6/91% in SCT group [p value < 0.001]. Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group [p value < 0.001] compared with the animals in the HF group

Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters

Improvement of tissue survival of skin flaps by 5 alpha-reductase inhibitors: possible involvement of nitric oxide and inducible nitric oxide synthase

Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5alpha-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase [iNOS] in graft survival mediated by these agents. A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid [100 mg/flap]; 3, finasteride [1 mg/flap]; 4, injection of L-N[G]-nitroarginine methyl ester [L-NAME] [i.p., 20 mg/kg]; 5, L-NAME [20 mg/kg, i.p.] + azelaic acid [100 mg/flap, topical]; 6, L-NAME [20 mg/kg, i.p.] + finasteride [1 mg/flap, topical]. Tissue survival, level of nitric oxide, and iNOS expression in groups were measured. Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide [NO] levels in graft tissue [P < 0.05]. These increases in iNOS expression and NO level were associated with higher survival of the graft tissue. It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps

Noscapine antagonizes vasoconstrictor action of bradykinin in isolated human umbilical artery

It has been demonstrated that noscapine, an antitussive opioid alkaloid, could antagonize bradykinin-induced responses such as bradykinin effects in guinea-pig ileum, cough induced by bradykinin receptor agonist and angiotensin converting enzyme inhibitors, and brain damage after brain edema both in neonatal rat model and in patients with stroke. In the present study, the effect of noscapine on bradykinin-induced constriction of human umbilical artery was investigated. Segments of human umbilical cords were obtained from women with normal full term pregnancies. Concentration-response curves for bradykinin [1-1000 nM] were constructed in the absence and presence of noscapine [1-1000 nM]. To show the specificity of noscapine for bradykinin-induced constriction in the tissue, the effect of noscapine [10 pM] on vasoconstriction produced by histamine were also examined. The results showed that noscapine could antagonize the constriction produced by bradykinin in human umbilical artery. It was also demonstrated that noscapine was capable of reducing histamine-induced contractile response. It is concluded that noscapine can antagonize bradykinin-induced constriction of human umbilical artery in a nonspecific manner. Thus, noscapine is likely to find a clinical application in pathologic conditions accompanied by higher vascular sensitivity to bradykinin in pregnancy