No abstract

Ayahuasca can be described as inducing changes in the perceptual, affective, cognitive, and somatic spheres, with a combination of stimulatory and visual psychoactive effects of longer duration and milder intensity than those previously reported for intravenously administered DMT.

Slices of developing brain tissue can be grown for several weeks as so-called organotypic slice cultures. Here we summarize and review studies using hippocampal slice cultures to investigate mechanisms and treatment strategies for the neurodegenerative disorders like stroke (cerebral ischemia), Alzheimer's disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic brain injury (TBI) and neurogenesis are included. For cerebral ischemia, experimental models with oxygen-glucose deprivation (OGD) and exposure to glutamate receptor agonists (excitotoxins) are reviewed. For epilepsia, focus is on induction of seizures with effects on neuronal loss, axonal sprouting and neurogenesis. For Alzheimer's disease, the review centers on the use of beta-amyloid (Abeta) in different models, while the section on repair is focused on neurogenesis and cell migration. The culturing techniques, set-up of models, and analytical tools, including markers for neurodegeneration, like the fluorescent dye propidium iodide (PI), are reviewed and discussed. Comparisons are made between hippocampal slice cultures and other in vitro models using dispersed cell cultures, experimental in vivo models, and in some instances, clinical trials. New techniques including slice culturing of hippocampal tissue from transgenic mice as well as more mature brain tissue, and slice cultures coupled to microelectrode arrays (MEAs), on-line biosensor monitoring, and time-lapse fluorescence microscopy are also presented.

In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the need for EPO-like compounds with selective neuroprotective actions. One such compound, devoid of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-D-aspartate (NMDA) excitotoxicity. Hippocampal slice cultures were pretreated for 24 h with 100 IU/ml EPO (= 26 nM) or 26 nM CEPO before OGD or NMDA lesioning. Exposure to EPO and CEPO continued during OGD and for the next 24 h until histology, as well as during the 24 h exposure to NMDA. Neuronal cell death was quantified by cellular uptake of propidium iodide (PI), recorded before the start of OGD and NMDA exposure and 24 h after. In cultures exposed to OGD or NMDA, CEPO reduced PI uptake by 49 ± 3 or 35 ± 8%, respectively, compared to lesion-only controls. EPO reduced PI uptake by 33 ± 5 and 15 ± 8%, respectively, in the OGD and NMDA exposed cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of α-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least as efficient neuroprotectant as EPO when excitotoxicity is modeled in mouse hippocampal slice cultures.

Eighty-six patients were treated with an implantable cardioverter defibrillator (ICD) because of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). In 27 patients an epicardial system was used, in 59 patients a transvenous system with a subcutaneous patch electrode was implanted. During a mean follow-up time of 17 +/- 9 months, inappropriate activations of the ICD due to supraventricular tachycardia were documented by Holter monitoring in 14 patients (16%). In 8 patients paroxysmal atrial fibrillation (AF), in 2 patients chronic AF, in 1 patient atrial flutter, and in 3 patients sinus tachycardia triggered antitachycardia pacing functions (12 patients) or internal defibrillation (2 patients). In 3 patients (5%) VT was induced by inappropriate antitachycardia pacing. In an additional 18 patients (21%) inappropriate activation of antitachycardia functions due to atrial tachyarrhythmias were suspected based on telemetry readouts or the patient's history. Inappropriate activation of ICD therapy triggered by intermittent supraventricular tachyarrhythmias is common. Further improvements of detection algorithms for supraventricular tachycardia are required in future device generations.