In mouse hippocampal CA1 pyramidal neurons, the activity of synaptic small-conductance Ca2+-activated K+ channels type 2 (SK2 channels) provides a negative feedback on N-methyl-d-aspartate receptors (NMDARs), reestablishing Mg2+ block that reduces Ca2+ influx. The well-established role of NMDARs in ischemia-induced excitotoxicity led us to test the neuroprotective effect of modulating SK2 channel activity following cerebral ischemia induced by cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Administration of the SK channel positive modulator, 1-ethyl-benzimidazolinone (1-EBIO), significantly reduced CA1 neuron cell death and improved CA/CPR-induced cognitive outcome. Electrophysiological recordings showed that CA/CPR-induced ischemia caused delayed and sustained reduction of synaptic SK channel activity, and immunoelectron microscopy showed that this is associated with internalization of synaptic SK2 channels, which was prevented by 1-EBIO treatment. These results suggest that increasing SK2 channel activity, or preventing ischemia-induced loss of synaptic SK2 channels, are promising and novel approaches to neuroprotection following cerebral ischemia.

Cerebellar Purkinje cells (PC) are particularly vulnerable to ischemic injury and excitotoxicity, although the molecular basis of this sensitivity remains unclear. We tested the hypothesis that ischemia causes rapid down‐regulation of GABAA receptors in cerebellar PC, thereby increasing susceptibility to excitotoxicity. Oxygen‐glucose deprivation (OGD) caused a decline in functional GABAA receptors, within the first hour of re‐oxygenation. Decreased amplitude of miniature inhibitory post‐synaptic potentials confirmed that OGD caused a significant decrease in functional synaptic GABAA receptors and quantitative Western blot analysis demonstrated the loss of GABAA receptor current was associated with a decline in total receptor protein. Interestingly, the potent neuroprotectant allopregnanolone (ALLO) prevented the decline in GABAA receptor current and protein. Consistent with our in vitro data, global ischemia in mice caused a significant decline in total cerebellar GABAA receptor protein and PC specific immunoreactivity. Moreover, ALLO provided strong protection of PC and prevented ischemia‐induced decline in GABAA receptor protein. Our findings indicate that ischemia causes a rapid and sustained loss of GABAA receptors in PC, whereas ALLO prevents the decline in GABAA receptors and protects against ischemia‐induced damage. Thus, interventions which prevent ischemia‐induced decline in GABAA receptors may represent a novel neuroprotective strategy.

P Pu ur rp po os se e: : To review six cases of Brugada syndrome presenting for insertion of a cardioverter-defibrillator under general anesthesia.C Cl li in ni ic ca al l f fe ea at tu ur re es s: : All patients had a history of syncope, ST segment elevation in the right precordial lead of the electrocardiogram (ECG) which became prominent after a pilsicainide challenge test. Routine monitors, right precordial lead of the ECG and an external defibrillator were installed prior to anesthesia. We administered propofol/midazolam for induction, and propofol/sevoflurane combined with fentanyl for maintenance of anesthesia. Atropine and ephedrine were administered to decrease vagal tone. No ECG change or arrhythmia was observed perioperatively. After the successful implantation of the defibrillator, all patients were discharged without any adverse event.C Co on nc cl lu us si io on n: : By avoiding agents or conditions that may exacerbate Brugada syndrome during anesthesia, we were able to manage the patients uneventfully for implantation of a cardioverter-defibrillator. Objectif Conclusion : En évitant les médicaments ou les conditions qui pourraient exacerber le syndrome de Brugada pendant l'anesthésie, nous avons pu procéder sans incident à l'implantation d'un défibrillateur à synchronisation automatique.RUGADA syndrome is a distinct form of an arrhythmic disease characterized by right bundle branch block and ST segment elevation in the right precordial leads (V1-V3) of the electrocardiogram (ECG). 1 This syndrome is clinically important because of the high incidence of sudden death by ventricular fibrillation (VF) without any structural heart disease, and is seen especially in the Asian populations including Japanese people. 2 Recently, it has been demonstrated that Brugada syndrome is genetically linked to the mutation of the alpha subunit of the sodium channel gene, SCN5A, 3 and the use of certain anti-arrhythmic sodium channel blockers (class IA and IC) accentuates the ECG manifestations. 4 To date, an implantable cardioverter-defibrillator (ICD) is the sole medical intervention which effectively protects patients with Brugada syndrome from sudden cardiac death. 5 Although a few single case reports of general anesthesia have been published, [6][7][8] there is no report of general anesthesia in a series of patients with Brugada syndrome. We herein report six patients with Brugada syndrome who underwent implantation of an ICD under general anesthesia.

There have been no reports on acute pulmonary embolism (APE) after earthquakes. Our aim was to clarify the actual the occurrence of APE following the 2004 Mid Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE after the event. We sent questionnaires to 122 hospitals in the Niigata Prefecture after the earthquake. Cities, towns, and villages in the prefecture were classified into two areas (high evacuee rate area, and low evacuee rate area) due to the mean ratio of evacuees to the overall population during 1 week immediately after the earthquake. A rate of 5% and higher was encountered for the high evacuee rate area and a rate of < 5% was encountered for the low evacuee rate area. Ten out-of-hospital cases of APE (seven in the high evacuee rate area and three in the low evacuee rate area) were diagnosed within the first month after the earthquake. The relative risk of APE was high in the high evacuee rate area (13.09; P = 0.0002) and also higher in women (8.55; P = 0.04). All patients in the high evacuee rate area had stayed in their automobiles for long periods of time, but none had done so in the low evacuee rate area ( P = 0.008).

Allopregnanolone (ALLO) is a neurosteroid that has many functions in the brain, most notably neuroprotection and modulation of gamma-amino butyric acid (GABA) neurotransmission. Using a mouse model of cardiac arrest and cardiopulmonary resuscitation, we have previously demonstrated that ALLO protects cerebellar Purkinje cells (PCs) from ischemia in a GABAA receptor-dependent manner. In this study we examined the effect of sex on ALLO neuroprotection, observing that low dose ALLO (2 mg/kg) provided greater neuroprotection in females compared to males. At a higher dose of ALLO (8 mg/kg), both sexes were significantly protected from ischemic damage. Using an acute cerebellar slice preparation, whole cell voltage clamp recordings were made from PCs. Spontaneous inhibitory postsynaptic currents (IPSCs) were analyzed and the response to physiological ALLO (10 nM) was significantly greater in female PCs compared to male. In contrast, recordings of miniature IPSCs, did not exhibit a sex difference in response to ALLO, suggesting that ALLO affects males and females differentially through a mechanism other than binding postsynaptic GABAA receptors. We conclude that the female brain has greater sensitivity to ALLO mediated potentiation of GABAergic neurotransmission, contributing to increased neuroprotection.