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BackgroundFocal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process.MethodsA penicillin-induced motor epileptic model in adult male C57BL/6 J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway.ResultsFirst, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity.ConclusionSTN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future.

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Using a best variable to scale glomerular filtration rate (GFR) is important for clinical practice. The variables, estimated by equations regressed from a healthy population, are usually used in scaling GFR of renal patients. However, because the predicted variables may deviate in renal patients, it is necessary to verify whether these variables can be used to reduce the variability of GFR of renal patients. This study was designed to use repeated measures analyses to identify the best variable for scaling GFR of renal patients.Patients with non-obstructive renal diseases were enrolled in this study. The absolute GFRs of (99m)Tc-DTPA renography (gGFR) and plasma clearance (pGFR) were measured. The indices relating to between-subjects variability, such as Passing and Bablok regression, intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) were used to identify the best variable from body surface area (BSA), extracellular fluid volume (ECV), lean body mass (LBM), total body water (TBW), body mass index (BMI), and metabolic rate (MR).For the scaled indices related to between-subjects variability, ICC and CCC identified the same ranking sequence (BMILBMB(B; Boer)LBMJ(J; James)TBWECVB(B; Bird)ECVS(S; Silva)BSAMR). In the Passing and Bablok regression, the ratio of residual standard deviation to pooled standard deviation (RSD/PSD) produced the same ranking sequence as that identified by ICC and CCC.The estimated metabolic rate can explain most between-subjects variability of GFR, and seems to be the best variable for scaling GFR of renal patients.

The effect of salicylaldoxime, 2-(OH)C 6 H 4 CH=NOH, on the resting membrane potential and action potential characteristics was studied using isolated right ventricular strips from rat heart. Salicylaldoxime (1-3 mM) reversibly hyperpolarized the cells, increased action potential amplitude, decreased the maximal rate of rise (V max ) and prolonged duration. The prolongation of the action potential produced by 1 mM salicyaldoxime could not be reversed with isoprenaline (10 μM). Salicyalaldoxime (0.3-1 mM) had no effect on the Ca 2+ -dependent slow action potential for periods up to 60 min. Initial exposure to 3 mM salicylaldoxime produced no changes in the slow action potential, but after 30 min. there was a gradual reduction in amplitude. This effect was completely reversible within 10-15 min. of washout. These data suggest that salicyaladoxime can block Na + , K + and Ca 2+ currents in rat cardiac muscle. Furthermore, it appears that the slow inward Ca 2+ current, as measured by the slow action potential, may be sensitive to a dephoshorylating action of this oxime.