Exendin-4 Pretreatment Attenuates Kainic Acid-Induced Hippocampal Neuronal Death.

Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that protects against brain injury. However, little is known about the effect of Ex-4 on kainic acid (KA)-induced seizures and hippocampal cell death. Therefore, this study evaluated the neuroprotective effects of Ex-4 pretreatment in a mouse model of KA-induced seizures. Three days before KA treatment, mice were intraperitoneally injected with Ex-4. We found that Ex-4 pretreatment reversed KA-induced reduction of GLP-1R expression in the hippocampus and attenuated KA-induced seizure score, hippocampal neuronal death, and neuroinflammation. Ex-4 pretreatment also dramatically reduced hippocampal lipocalin-2 protein in KA-treated mice. Furthermore, immunohistochemical studies showed that Ex-4 pretreatment significantly alleviated blood-brain barrier leakage. Finally, Ex-4 pretreatment stimulated hippocampal expression of phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB), a known target of GLP-1/GLP-1R signaling. These findings indicate that Ex-4 pretreatment may protect against KA-induced neuronal damage by regulating GLP-1R/CREB-mediated signaling pathways.

Nitrogen Stimulates Microcystis-Dominated Blooms More than Phosphorus in River Conditions That Favor Non-Nitrogen-Fixing Genera.

Despite the implementation of intensive phosphorus reduction measures, periodic outbreaks of cyanobacterial blooms in large rivers remain a problem in Korea, raising the need for more effective solutions to reduce their occurrence. This study sought to evaluate whether phosphorus or nitrogen limitation is an effective approach to control cyanobacterial (Microcystis) blooms in river conditions that favor this non-nitrogen-fixing genus. These conditions include nutrient enrichment, high water temperature, and thermal stratification during summer. Mesocosm bioassays were conducted to investigate the limiting factors for cyanobacterial blooms in a river reach where severe Microcystis blooms occur annually. We evaluated the effect of five different nitrogen (3, 6, 9, 12, and 15 mg/L) and phosphorus (0.01, 0.02, 0.05, 0.1, and 0.2 mg/L) concentrations on algae growth. The results indicate that nitrogen treatments stimulated cyanobacteria (mostly Microcystis aeruginosa) more than phosphorus. Interestingly, phosphorus additions did not stimulate cyanobacteria, although it did stimulate Chlorophyceae and Bacillariophyceae. We conclude that phosphorus reduction might have suppressed the growth of Chlorophyceae and Bacillariophyceae more than that of cyanobacteria; therefore, nitrogen or at least both nitrogen and phosphorus control appears more effective than phosphorus reductions alone for reducing cyanobacteria in river conditions that are favorable for non-nitrogen-fixing genera.

Determinants of embolic risk during angioplasty and stenting: neurologic symptoms and coronary artery disease increase embolic risk.

BACKGROUND: Carotid angioplasty and stenting (CAS) has proven to be a potential alternative to carotid endarterectomy in the treatment of severe carotid disease. Patient selection has emerged as a means of optimizing the outcomes of CAS. OBJECTIVE: To determine whether the presence of preprocedural neurologic symptoms and having a history of coronary artery disease (CAD) are associated with greater embolic risk during CAS through analysis of the embolic debris captured within protective filters. METHODS: A total of 233 consecutive CAS procedures were performed between 2003 and 2009. Particles of embolic debris within the filters were quantified by photomicroscopy and video imaging software. Particulate size was determined by measuring the length along the longest axis. Preprocedural neurologic symptoms included transient ischemic attack, cerebrovascular accident, and amaurosis fugax. History of CAD included prior myocardial infarction, coronary artery bypass grafting, congestive heart failure, or abnormal stress test. RESULTS: Of the 137 (58.8%) filters that were analyzed (mean age, 71.3 ± 9.1 years, 56.9% male), 52 (38.0%) and 80 (58.4%) filters were from symptomatic and CAD patients, respectively. Filters of symptomatic (S) patients contained both a greater number and larger mean particle size compared with those of asymptomatic (AS) patients (S: 15.8 ± 13.5 particles vs. AS: 9.8 ± 8.7 particles, P = 0.002; S: 507 ± 389 µm vs. AS: 398 ± 181 µm, P = 0.03; respectively). Filters from CAD patients also had a greater number of particles, but trended toward smaller minimum size than those in non-CAD patients (CAD: 14.4 ± 12.8 particles vs. non-CAD: 8.8 ± 7.4 particles, P = 0.002; CAD: 167 ± 172 µm vs. 228 ± 203 µm, P = 0.06). CONCLUSIONS: These findings suggest that the presence of preprocedural neurologic symptoms and a history of CAD are associated with increased embolization during CAS. Therefore, the benefit of carotid stenting should be tempered by the potential for increased perioperative events in both symptomatic and CAD patients.