Brain slices

The purpose of this study was to investigate the anticonvulsant activity of the volatile oil of nutmeg, the dried seed kernel of Myristica fragrans Houtt, using well-established animal seizure models and to evaluate its potential for acute toxicity and acute neurotoxicity. The volatile oil of nutmeg (nutmeg oil) was tested for its effects in maximal electroshock, subcutaneous pentylenetetrazole, strychnine and bicuculline seizure tests. All the experiments were performed at the time of peak effect of nutmeg oil. Nutmeg oil showed a rapid onset of action and short duration of anticonvulsant effect. It was found to possess significant anticonvulsant activity against electroshock-induced hind limb tonic extension. It exhibited dose dependent anticonvulsant activity against pentylenetetrazole-induced tonic seizures. It delayed the onset of hind limb tonic extensor jerks induced by strychnine. It was anticonvulsant at lower doses, whereas weak proconvulsant at a higher dose against pentylenetetrazole and bicuculline induced clonic seizures. Nutmeg oil was found to possess wide therapeutic margin, as it did not induce motor impairment when tested up to 600 µL/kg in the inverted screen acute neurotoxicity test. Furthermore, the LD50 (2150 µL/kg) value was much higher than its anticonvulsant doses (50–300 µL/kg). The results indicate that nutmeg oil may be effective against grand mal and partial seizures, as it prevents seizure spread in a set of established animal models. Slight potentiation of clonic seizure activity limits its use for the treatment of myoclonic and absence seizures. Copyright © 2008 John Wiley & Sons, Ltd.

This study has tested the feasibility of using physical delivery methods, employing static and oscillating field "magnetofection" techniques, to enhance magnetic nanoparticle-mediated gene transfer to rat oligodendrocyte precursor cells derived for transplantation therapies. These cells are a major transplant population to mediate repair of damage as occurs in spinal cord injury and neurological diseases such as multiple sclerosis. We show for the first time that magnetic nanoparticles mediate effective transfer of reporter and therapeutic genes to oligodendrocyte precursors; transfection efficacy was significantly enhanced by applied static or oscillating magnetic fields, the latter using an oscillating array employing high-gradient NdFeB magnets. The effects of oscillating fields were frequency-dependent, with 4 Hz yielding optimal results. Transfection efficacies obtained using magnetofection methods were highly competitive with or better than current widely used nonviral transfection methods (e.g., electroporation and lipofection) with the additional critical advantage of high cell viability. No adverse effects were found on the cells' ability to divide or give rise to their daughter cells, the oligodendrocytes-key properties that underpin their regeneration-promoting effects. The transplantation potential of transfected cells was tested in three-dimensional tissue engineering models utilizing brain slices as the host tissue; modified transplanted cells were found to migrate, divide, give rise to daughter cells, and integrate within host tissue, further evidencing the safety of the protocols used. Our findings strongly support the concept that magnetic nanoparticle vectors in conjunction with state-of-the-art magnetofection strategies provide a technically simple and effective alternative to current methods for gene transfer to oligodendrocyte precursor cells.

The purpose of this study was to investigate the anticonvulsant activity of the volatile oil of nutmeg, the dried seed kernel of Myristica fragrans Houtt, using well-established animal seizure models and to evaluate its potential for acute toxicity and acute neurotoxicity. The volatile oil of nutmeg (nutmeg oil) was tested for its effects in maximal electroshock, subcutaneous pentylenetetrazole, strychnine and bicuculline seizure tests. All the experiments were performed at the time of peak effect of nutmeg oil. Nutmeg oil showed a rapid onset of action and short duration of anticonvulsant effect. It was found to possess significant anticonvulsant activity against electroshock-induced hind limb tonic extension. It exhibited dose dependent anticonvulsant activity against pentylenetetrazole-induced tonic seizures. It delayed the onset of hind limb tonic extensor jerks induced by strychnine. It was anticonvulsant at lower doses, whereas weak proconvulsant at a higher dose against pentylenetetrazole and bicuculline induced clonic seizures. Nutmeg oil was found to possess wide therapeutic margin, as it did not induce motor impairment when tested up to 600 µL/kg in the inverted screen acute neurotoxicity test. Furthermore, the LD50 (2150 µL/kg) value was much higher than its anticonvulsant doses (50–300 µL/kg). The results indicate that nutmeg oil may be effective against grand mal and partial seizures, as it prevents seizure spread in a set of established animal models. Slight potentiation of clonic seizure activity limits its use for the treatment of myoclonic and absence seizures. Copyright © 2008 John Wiley & Sons, Ltd.

Neuronal signaling, plasticity, and pathologies in CA1 hippocampal neurons are all intimately related to the redox environment and, thus tissue oxygenation. This study tests the hypothesis that hyperoxic superfusate (95% O(2)) causes a time-dependent increase in superoxide anion (*O(2)(-)) production in CA1 neurons in slices, which will decrease as oxygen concentration is decreased. Hippocampal slices (400 microm) from weaned rats were incubated with the fluorescent probe dihydroethidium (DHE), which detects intracellular *O(2)(-) production. Slices were loaded for 30 min using 10 microM DHE and maintained using one-sided superfusion or continuously loaded using 2.5 microM DHE and maintained using two-sided superfusion (36 degrees C). Continuous loading of DHE and two-sided superfusion gave the highest temporal resolution measurements of *O(2)(-) production, which was estimated by the increase in fluorescence intensity units (FIUs) per minute (FIU/min +/- SE) over 4 h. Superoxide production (2.5 microM DHE, 2-sided superfusion) was greatest in 95% O(2) (6.6 +/- 0.4 FIU/min) and decreased significantly during co-exposure with antioxidants (100 microM melatonin, 25 microM MnTMPyP) and lower levels of O(2) (60, 40, and 20% O(2) at 5.3 +/- 0.3, 3.3 +/- 0.1, and 1.6 +/- 0.2 FIU/min, respectively). CA1 cell death after 4 h (ethidium homodimer-1 staining) was greatest in 95% O(2) and lowest in 40 and 20% O(2). CA1 neurons generated evoked action potentials in 20% O(2) for >4 h, indicating viability at lower levels of oxygenation. We conclude that .O(2)(-) production and cell death in CA1 neurons increases in response to increasing oxygen concentration product (= PO(2) x time). Additionally, lower levels of oxygen (20-40%) and antioxidants should be considered to minimize superoxide-induced oxidative stress in brain slices.

In 1927, the German popular science magazine Die Koralle published an article entitled "The Library of Brains." The article was about the Kaiser Wilhelm Institute for Brain Research in Berlin, established in 1914 as the continuation of the "Neurological Central Station" founded by Oskar Vogt (1870-1959) in 1898. The library metaphor plays on the huge collection of human and animal brains Oskar and his wife C ecile (1875-1862) had gathered over several decades. For examination, the brains were cut into paper-thin slices and embedded in paraffin: from one single organ, up to 30,000 slices could be extracted, which were to be "read" and studied like the pages of a book. In this chapter, we take the metaphor at face value, arguing that Vogt's institute actually functioned as a library. Numerous publications have emphasized the role of the Vogts and, in particular, of the brain collection for the constitution of modern neuroscience. The "library," however, has never been closely investigated. How was it designed? How was it filled? According to which criteria were the brains collected and ordered? How did the order and the collection itself reflect the Vogts' research program? Through a detailed investigation of the collection and the Vogt Archive, we will examine this "library" and reconstruct the order of the Vogt brains. The mutual relationship between collecting, sorting, examining and publishing about the brain will be discussed.

Keywords Oskar Vogt, C ecile Vogt, Kaiser Wilhelm Institute for Brain Research, Brain collections, Brain slices, Serial sectioning, History of neuroanatomy, History of microtomy, Brain-reading metaphor

Obesity is considered as a risk factor for mood disorders including depression. Nevertheless, the mechanisms underlying this association are not clearly understood. To address this issue, we investigated the impact of high-fat (HF)-diet-induced obesity on depressive-like behavior and on serotonin (5-HT)-dependent Akt/glycogen synthase kinase 3β (GSK3β) signaling in the dentate gyrus (DG) of the hippocampus, which has been associated with mood regulation. We first showed that a HF diet induced significant overweight and hyperglycemia as well as a depressive-like behavior in adult Wistar rats. By using an ex vivo approach on brain slices, we demonstrated that 5-HT activates the Akt/GSK3β cascade in the DG of control chow (C) diet-fed animals and that a 16-week HF diet feeding abolishes this activation, concurrently with a desensitization of leptin and insulin signaling in the same region. Furthermore, depressive-like behavior inversely correlated with 5-HT-induced phosphorylation of GSK3β in the subgranular neurons of the DG. Interestingly, a substitution of HF with C diet for 6 weeks induced a total loss of depressive symptoms, whereas body weight and glycemia remained significantly higher compared to control rats. In addition, food restoration led to a recovery of the Akt/GSK3β signaling pathway activation in the DG. In parallel, we observed a negative correlation between body weight and cell proliferation in the subgranular zone of the DG. To conclude, we provide evidence for a desensitization of 5-HT-induced Akt/GSK3β signaling and an impaired cell proliferation in the DG by HF diet, suggesting novel molecular mechanisms linking obesity to depression.

... Phenytoin was synthesized in 1908, and was recognized as a first non sedating antiepileptic drug after the pioneering studies of Merritt and Putnam using an electroshock-induced seizure model in cats [74-76]. Since then electroshock-induced seizure model has been used ...

Esfenvalerate belongs to the pyrethroid group of insecticides which display significant selective toxicity against insects compared to mammalian species, nevertheless, they may pose health risks, especially in case of accidental exposure. The aim of the present study was to model the effect of acute, relatively high-dose exposure of the esfenvalerate-containing formulation Sumi-Alpha?. Eventual functional alterations in the central nervous system and in the gastrointestinal tract were studied on in vitro tissue preparations at different delays after intragastric administration to rats. Neuronal effects were characterized by field potential recording in cortical and hippocampal brain slices, while gastrointestinal effects were examined by analyzing the motility and excitability of isolated ileum segments. On the brain slices originating from esfenvalerate-treated animals, changes in excitability of both inhibitory and excitatory type could be observed. Voltage thresholds necessary to evoke responses in neocortex slices were elevated, and population spike amplitudes were lower in hippocampal slices. However, epileptiform potentials with pronounced late components were also observed. A decreased long-term potentiation (LTP) could be seen in both brain areas after esfenvalerate treatment. Seizure susceptibility of the slices was not significantly altered, but tended to be somewhat higher in slices originating from treated rats. In ileum segments, both spontaneous and acetyl-choline (ACh)-elicited contractions were modified by treatment. Esfenvalerate raised the amplitude of contractions in the low ACh concentration range. However, the solvent xylene also considerably contributed to the detected changes. We can conclude that a relatively high, single oral dose of Sumi-Alpha? exerted mild and temporary effects on the elementary brain functions and intestine functions of the rat.

Astrocytes are a major transplant cell population to promote neural repair in a range of pathological condi- tions. In this context, the development of robust methods to label neural transplant populations (for subse- quent detection and cell tracking in vivo) is key for translational applications. Magnetic iron oxide nanoparticles (MNP)-based vector systems offer a range of advantages for neural cell transplantation, notably, as contrast agents for magnetic resonance imaging, which allows for MNP-labeled cells to be detected using minimally invasive methods. Additionally, MNPs have other key features such as safety, the potential for linking with genetic material/drugs, and magnetic cell targeting. Therefore, MNPs can potentially be devel- oped as a multipurpose nanoplatform for neural cell transplantation. The feasibility of labeling astrocytes derived for transplantation with MNPs has not been assessed to date. Here, we have established simple protocols to safely label astrocytes with MNPs; the survival and differentiation of labeled cells was assessed in threedimensional neural tissuearrays.Additionally,wehaveestablished themajor mechanisms of MNP uptake by astrocytes.