Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

miR-203 protects microglia mediated brain injury by regulating inflammatory responses via feedback to MyD88 in ischemia

Much evidence demonstrates that microglia mediated inflammatory responses play an important role in brain injury in ischemia. miRNA is the important factor in regulation of inflammation. However, the effect of miRNA in microglia mediated inflammatory responses has not been well studied. In the study, we demonstrate that miR-203 negatively regulates ischemia induced microglia activation by targeting MyD88, an important adapter protein involved in most Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) pathways. Through negative feedback, enforced expression of miR-203 or MyD88 siRNA silencing inhibits downstream NF-κβ signaling and microglia activation, thereby alleviating neuronal injury. These findings reveal that miR-203 represents a novel target regulating neuroinflammation and brain injury, thus offering a new therapeutical strategy for cerebral hypoxic diseases.     

Experimental study on prophylactic effects of vardenafil in ischemia–reperfusion model with intestinal volvulus injury in rats

AimAn experimental study was performed to evaluate the effects of Vardenafil on ischemia–reperfusion (I/R) injury in an experimental volvulus model by histochemical and biochemical methods.Materials and methodsThirty-five male Wistar rats were divided in five groups (n = 7). In Group 1, a 5 cm segment of small intestine 2 cm proximal to cecum was excised to have a control group. In the second group, 5 cm segment of small intestine 2 cm proximal to cecum was rotated 360° clockwise direction and sutured with 4/0 polyglactin to generate an experimental model of volvulus. At the end of 2 h of ischemia, the same intestinal segment was sampled. In group 3, after achieving ischemia similar to group 2, two hours of reperfusion injury was obtained by removing the sutures. Rats in Group 4 received vardenafil after 1.5 h of ischemia and then 2 h of reperfusion. And finally, in Group 5, vardenafil was administered 2 h before laparotomy and 5 cm of intestine was removed without I/R injury. Intestinal segments were evaluated for total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) with biochemical and histopathological analysis.ResultsSerum TOS levels and OSI were not significantly different between groups (p = 0.910, P = 0,43 respectively). The serum TAS level was decreased in group 3 as compared to vardenafil groups 4 and 5, without a statistical significance (p = 0.428). In histopathologic analysis, we found that vardenafil, partially reduced I/R injury. The villus structure was preserved but, congestion and inflammation were moderate.ConclusionVardenafil partially reduced I/R injury histopathologically on intestine. Our study shows that it does not have statistically antioxidant effect on intestinal I/R injury in experimental model of volvulus. However, effects of vardenafil in I/R injury of liver, kidney, heart, testis, over and brain which were cited in literature were not confirmed with I/R injury on intestine.     

Deficiency of anti-inflammatory cytokine IL-4 leads to neural hyperexcitability and aggravates cerebral ischemia–reperfusion injury

Systematic administration of anti-inflammatory cytokine interleukin 4 (IL-4) has been shown to improve recovery after cerebral ischemic stroke. However, whether IL-4 affects neuronal excitability and how IL-4 improves ischemic injury remain largely unknown. Here we report the neuroprotective role of endogenous IL-4 in focal cerebral ischemia–reperfusion (I/R) injury. In multi-electrode array (MEA) recordings, IL-4 reduces spontaneous firings and network activities of mouse primary cortical neurons. IL-4 mRNA and protein expressions are upregulated after I/R injury. Genetic deletion of Il-4 gene aggravates I/R injury in vivo and exacerbates oxygen-glucose deprivation (OGD) injury in cortical neurons. Conversely, supplemental IL-4 protects Il-4^−/− cortical neurons against OGD injury. Mechanistically, cortical pyramidal and stellate neurons common for ischemic penumbra after I/R injury exhibit intrinsic hyperexcitability and enhanced excitatory synaptic transmissions in Il-4^−/− mice. Furthermore, upregulation of Nav1.1 channel, and downregulations of KCa3.1 channel and α6 subunit of GABA_A receptors are detected in the cortical tissues and primary cortical neurons from Il-4^−/− mice. Taken together, our findings demonstrate that IL-4 deficiency results in neural hyperexcitability and aggravates I/R injury, thus activation of IL-4 signaling may protect the brain against the development of permanent damage and help recover from ischemic injury after stroke.     

Endovascular Treatment Outcome and CT Angiography Findings in Acute Basilar Artery Occlusion with and without Underlying Intracranial Atherosclerotic Stenosis

PurposeTo compare clinical characteristics and treatment outcomes of intra-arterial thrombectomy (IAT) in acute basilar artery occlusion (BAO) with and without underlying intracranial atherosclerotic stenosis (ICAS) and to investigate the usefulness of preprocedural CT angiography findings in the diagnosis of ICAS.Materials and MethodsTwenty patients who received IAT for acute BAO between September 2014 and March 2019 were included. Additional therapies such as angioplasty, stent placement, and tirofiban infusion were provided while treating ICAS. Clinical and angiographic results of treatment were recorded. Preprocedural CT angiography findings in ICAS and non-ICAS groups were compared to assess (i) basilar tip opacification, (ii) partial occlusion, (iii) presence of convex border, (iv) occlusion segment longer than two thirds of the basilar artery or 20 mm, (v) dense basilar artery, and (vi) wall calcification in the occluded segment.ResultsAmong the 20 patients (mean age, 71.3 y; mean stroke score, 24.8), optimal recanalization was achieved in 19 (95%). Three patients had good clinical outcomes. There were 6 patients with underlying ICAS. No difference was observed between ICAS and non-ICAS groups in terms of optimal angiographic recanalization and good outcome. On CT angiography, basilar tip occlusion (100% vs 29%), partial occlusion (100% vs 83%), and long occlusion length (100% vs 14%) significantly differed between the groups (P ≤ .01).ConclusionsIn acute BAO, underlying ICAS does not affect optimal recanalization rate or clinical outcome. Preprocedural CT angiography is a potentially useful tool to detect it.     

Outcomes of upper extremity interventions for chronic critical ischemia

Background

Critical hand ischemia owing to below-the-elbow atherosclerotic occlusive disease is relatively uncommon. The aim of this study was to examine the outcomes in patients presenting with critical ischemia owing to below-the-elbow arterial atherosclerotic disease who underwent nonoperative and operative management.