Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of glucocorticoid receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.     

Mechanistic insight,diagnosis, and treatment of ammonia‐induced hepatic encephalopathy

Hepatic encephalopathy is a neuropsychological syndrome due to biochemical disturbance of brain function in advanced liver disease patients. Diagnosis and treatment of the condition is very demanding and has negative toll on finances with increased healthcare utilization. The pathophysiology is not completely understood; however, there is evidence that ammonia plays an important role in the etiology. Conventional methods of solely relying on blood ammonia level to diagnose hepatic encephalopathy did not help much; likewise, the use of lactulose alone in treating hepatic encephalopathy has also been discouraged. This paper analyzed the current knowledge regarding the mechanism of how ammonia disrupts the normal brain function as well as the use of latest diagnosing tools including those under development to evaluate the neuropsychiatric state of patients and their quality of life. The efficacies of lactulose and rifaximin combination for short‐term and long‐term treatment in addition to nutritional interventions and other drugs undergoing clinical trials were also reviewed.     

Balloon Pulmonary Angioplasty for the Treatment of Nonoperable Chronic Thromboembolic Pulmonary Hypertension: Single-Center Experience with Low Initial Complication Rate

PurposeTo evaluate the safety and efficacy of balloon pulmonary angioplasty (BPA) for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH) patients during the initial experience of a single center.MethodsA total of 18 CTEPH patients (5 with residual pulmonary hypertension after pulmonary endarterectomy) were treated with BPA during the period 2014–2018 and were retrospectively reviewed. Mean age was 61 ± 19 years; 55% were female; mean pulmonary artery pressure was 44 ± 12 mmHg; cardiac output was 4.3 ± 1.0 l/min; and pulmonary vascular resistance was 8.4 ± 3.6 WU. Patients were evaluated by New York Heart Association functional class, 6-minute walk distance, N-terminal pro b-type natriuretic peptide, echocardiography, right heart catheterization, and before and after completions of BPA.ResultsA total of 91 procedures were performed, with a median number of 4 BPA sessions per patient (range, 2–8). There were no deaths or major complications requiring extracorporeal support or (non)invasive ventilation. The most common complication was self-limiting hemoptysis (3%). According to Society of Interventional Radiology classification, 4 mild, 4 moderate, and 1 severe adverse events were noted. Invasive hemodynamics significantly improved, with a cardiac index increase of 15% (P = .0333), decrease of mean pulmonary artery pressure of 30% (P = .0013), and decrease of pulmonary vascular resistance of 45% (P = .0048). Stroke volume index (P = .0171) and pulmonary arterial compliance (P = .0004) were also significantly enhanced.ConclusionsBPA significantly improves cardiopulmonary hemodynamics with an acceptable safety profile. Further studies assessing the long-term efficacy of BPA are required.