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Several comparison studies have suggested that kidney transplant (KT) could reduce stroke risk in patients with end-stage renal disease (ESRD). To avoid the selection criteria bias of using dialysis patients as control groups, we compared the risk of stroke between KT recipients and comparable propensity score-matched dialysis patients. We used Taiwan's National Health Insurance Research Database to identify patients with newly diagnosed ESRD between 2000 and 2009. We separated them into 2 groups: a KT group and a non-KT dialysis-only group. To evaluate the stroke outcome, we compared each patient with KT to a patient on dialysis without KT using propensity score matching. In total, 2735 KT recipients and 10,940 propensity score-matched dialysis patients were identified. The incidence rates of overall stroke were 9.1 and 23.4 per 1000 person-years in KT recipients and non-KT dialysis patients. Compared with the propensity score-matched dialysis patients, the patients who received KT exhibited significantly lower overall stroke risk, hemorrhagic stroke, and ischemic stroke, the adjusted hazard ratios were 0.37 (95% CI, 0.31–0.45), 0.19 (95% CI, 0.12–0.29), and 0.46 (95% CI, 0.37–0.56), respectively (all P <.001). Through a propensity score-matched cohort, this study confirms that KT is associated with a reduced risk of stroke more than dialysis alone in patients with newly diagnosed ESRD. • The incidence rates of stroke were 9.1 and 23.4 per 1000 person-years in Taiwanese kidney transplant recipients and dialysis patients. • The incidence rate of hemorrhagic stroke was lower than ischemic stroke in Taiwanese kidney transplant recipients. • Kidney transplant reduces the risk of stroke risk of patients with end-stage renal disease. [ABSTRACT FROM AUTHOR]

Evidence suggests that the glutamatergic system plays a crucial role in the pathophysiology and treatment of depression. This study investigates the effect of WAY208466, a 5-HT 6 receptor agonist exhibiting an antidepressant effect, on glutamate release from rat hippocampal nerve terminals (synaptosomes). WAY208466 inhibited the Ca 2+ -dependent release of glutamate that was evoked by exposing the synaptosomes to the potassium channel blocker 4-aminopyridine, and the selective 5-HT 6 receptor antagonist SB258585 blocked this phenomenon. The WAY208466-mediated inhibition of glutamate release was associated with a reduction of 4-aminopyridine-induced increase in the cytosolic free Ca 2+ concentration ([Ca 2+ ] C ) mediated via Ca v 2.2 (N-type) and Ca v 2.1 (P/Q-type) channels. WAY208466 did not alter the resting synaptosomal membrane potential or 4-aminopyridine-mediated depolarization; thus, the inhibition of the Ca 2+ influx could not be attributed to the decrease in synaptosomal excitability caused by 5-HT 6 receptor activation. Furthermore, the effect of WAY208466 on 4-aminopyridine-evoked glutamate release was prevented by a Gi/Go-protein inhibitor pertussis toxin, adenylate cyclase inhibitor SQ22536, and a protein kinase A inhibitor H89. These results suggest that WAY208466 acts at the 5-HT 6 receptors present in the hippocampal nerve terminals to suppress the Gi/Go-protein-coupled adenylate cyclase/protein kinase A cascade, which subsequently reduces the Ca 2+ influx via N- and P/Q-type Ca 2+ channels to inhibit the evoked glutamate release. This finding implicated a potential therapeutic role of 5-HT 6 receptor agonist in the treatment of depression and other neurological diseases associated with glutamate excitotoxicity. [ABSTRACT FROM AUTHOR]