Neuroprotective Properties of Topiramate in the Lithium- Pilocarpine Model of Epilepsy

ABSTRACT The lithium-pilocarpine model reproduces the main characteristics of human temporal lobe epilepsy. After status epilepticus (SE), rats exhibit a latent seizure-free phase characterized by development of extensive damage in limbic areas and occurrence of spontaneous recurrent seizures. Neuroprotective and antiepileptogenic effects of topiramate were investigated in this model. SE was induced in adult male rats by LiCl (3 mEq/kg) followed 20 h later by pilocarpine (25 mg/kg). Topiramate (10, 30, or 60 mg/kg) was injected at 1 and 10 h of SE. Injections were repeated twice a day for six additional days. Another group received two injections of diazepam on the day of SE and of vehicle for 6 days. Neuronal damage was assessed at 14 days after SE by cell counting on thionin-stained sections. Occurrence of spontaneous recurrent seizures (SRS) was videorecorded for 10 h per day in other groups of rats. In diazepam-treated rats, the number of neurons was dramatically reduced after SE in all subregions of hippocampus and layers II-IV of ventral cortices. At all doses, topiramate induced a 24 to 30% neuroprotection in layer CA1 of hippocampus (p Ͻ 0.05). In CA3b, the 30-mg/kg dose prevented neuronal death. All rats subjected to SE became epileptic. The latency (14 -17 days) to and frequency of SRS were similar in topiramate-and diazepam-treated rats. The high mortality in the 30 mg/kg topiramate group (84%) was possibly the result of interaction between lithium and topiramate. In conclusion, topiramate displayed neuroprotective properties only in CA1 and CA3 that were not sufficient to prevent epileptogenesis

Global and regional brain metabolic scaling and its functional consequences

Background: Information processing in the brain requires large amounts of metabolic energy, the spatial distribution of which is highly heterogeneous reflecting complex activity patterns in the mammalian brain. Results: Here, it is found based on empirical data that, despite this heterogeneity, the volume-specific cerebral glucose metabolic rate of many different brain structures scales with brain volume with almost the same exponent around -0.15. The exception is white matter, the metabolism of which seems to scale with a standard specific exponent -1/4. The scaling exponents for the total oxygen and glucose consumptions in the brain in relation to its volume are identical and equal to $0.86\pm 0.03$, which is significantly larger than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on body mass. Conclusions: These findings show explicitly that in mammals (i) volume-specific scaling exponents of the cerebral energy expenditure in different brain parts are approximately constant (except brain stem structures), and (ii) the total cerebral metabolic exponent against brain volume is greater than the much-cited Kleiber's 3/4 exponent. The neurophysiological factors that might account for the regional uniformity of the exponents and for the excessive scaling of the total brain metabolism are discussed, along with the relationship between brain metabolic scaling and computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen

The Depolarizing Action of GABA in Cultured Hippocampal Neurons Is Not Due to the Absence of Ketone Bodies

Two recent reports propose that the depolarizing action of GABA in the immature brain is an artifact of in vitro preparations in which glucose is the only energy source. The authors argue that this does not mimic the physiological environment because the suckling rats use ketone bodies and pyruvate as major sources of metabolic energy. Here, we show that availability of physiologically relevant levels of ketone bodies has no impact on the excitatory action of GABA in immature cultured hippocampal neurons. Addition of β-hydroxybutyrate (BHB), the primary ketone body in the neonate rat, affected neither intracellular calcium elevation nor membrane depolarizations induced by the GABA-A receptor agonist muscimol, when assessed with calcium imaging or perforated patch-clamp recording, respectively. These results confirm that the addition of ketone bodies to the extracellular environment to mimic conditions in the neonatal brain does not reverse the chloride gradient and therefore render GABA hyperpolarizing. Our data are consistent with the existence of a genuine “developmental switch” mechanism in which GABA goes from having a predominantly excitatory role in immature cells to a predominantly inhibitory one in adults

Petrogenesis of crustal wehrlites in the Oman ophiolite: Experiments and natural rocks

In the Wadi Haymiliyah of the Oman ophiolite (Haylayn block), discordant wehrlite bodies ranging in size from tens to hundreds of meters intrude the lower crust at different levels. We combined investigations on natural wehrlites from the Wadi Haymiliyah section with an experimental study on the phase relations in a wehrlitic system in order to constrain the petrogenesis of the crustal wehrlites of the Oman ophiolite. Secondary ion mass spectrometry analyses of clinopyroxenes from different wehrlite bodies imply that the clinopyroxenes were crystallized from tholeiitic, mid-ocean ridge (MORB)–type melts. The presence of primary magmatic amphiboles in some wehrlites suggests a formation under hydrous conditions. Significantly enhanced 87Sr/86Sr isotope ratios of separates from these amphiboles imply that the source of the corresponding magmatic fluids was either seawater or subduction zone–related. The experiments revealed that under wet conditions at relatively low temperatures, a MORB magma has the potential to produce wehrlite in the ocean crust by accumulation of early olivine and clinopyroxene. These show typically high Mg# which is a consequence of the oxidizing effect of the prevailing high aH2O. First plagioclases crystallizing after clinopyroxene under wet conditions are high in An content, in contrast to the corresponding dry system. Trace element compositions of clinopyroxenes of those wehrlites from the Moho transition zone are too depleted in HREE to be in equilibrium with present-day MORB, implying a genetic relation to the V2 lavas of the Oman ophiolite, which are interpreted to be the result of fluidenhanced melting of previously depleted mantle. We present a model on the petrogenesis of the crustal wehrlites in an upper mantle wedge above an initial, shallow subduction zone at the beginning of the intraoceanic thrusting

Hydrothermal origin of halogens at Home Plate, Gusev Crater

In the Inner Basin of the Columbia Hills, Gusev Crater is Home Plate, an 80 m platform of layered clastic rocks of the Barnhill class with microscopic and macroscopic textures, including a bomb sag, suggestive of a phreatomagmatic origin. We present data acquired by the Spirit Mars Exploration Rover by Alpha Particle X-Ray Spectrometer (APXS), Mössbauer Spectrometer, Miniature Thermal Emission Spectrometer (Mini- TES), and Panoramic Camera (Pancam) for the Barnhill class rocks and nearby vesicular Irvine class basalts. In major element concentrations (e.g., SiO2, Al2O3, MgO, and FeO*), the two rock classes are similar, suggesting that they are derived from a similar magmatic source. The Barnhill class, however, has higher abundances of Cl, Br, Zn, and Ge with comparable SO3 to the Irvine basalts. Nanophase ferric oxide (np ox) and volcanic glass were detected in the Barnhill class rocks by Mössbauer and Mini-TES, respectively, and imply greater alteration and cooling rates in the Barnhill than in the Irvine class rocks. The high volatile elements in the Barnhill class agree with volcanic textures that imply interaction with a briny groundwater during eruption and (or) by later alteration. Differences in composition between the Barnhill and Irvine classes allow the fingerprinting of a Na-Mg-Zn-Ge-Cl-Br (±Fe ± Ca ± CO2) brine with low S. Nearby sulfate salt soils of fumarolic origin may reflect fractionation of an acidic S-rich vapor during boiling of a hydrothermal brine at depth. Persistent groundwater was likely present during and after the formation of Home Plate

Subsurface hydrothermal processes and the bioenergetics of chemolithoautotrophy at the shallow-sea vents off Panarea Island (Italy)

The subsurface evolution of shallow-sea hydrothermal fluids is a function of many factors including fluid-mineral equilibria, phase separation, magmatic inputs, and mineral precipitation, all of which influence discharging fluid chemistry and consequently associated seafloor microbial communities. Shallow-sea vent systems, however, are understudied in this regard. In order to investigate subsurface processes in a shallow-sea hydrothermal vent, and determine how these physical and chemical parameters influence the metabolic potential of the microbial communities, three shallow-sea hydrothermal vents associated with Panarea Island (Italy) were characterized. Vent fluids, pore fluids and gases at the three sites were sampled and analyzed for major and minor elements, redox-sensitive compounds, free gas compositions, and strontium isotopes. The corresponding data were used to 1) describe the subsurface geochemical evolution of the fluids and 2) to evaluate the catabolic potential of 61 inorganic redox reactions for in situ microbial communities. Generally, the vent fluids can be hot (up to 135 °C), acidic (pH 1.9-5.7), and sulfidic (up to 2.5 mM H2S). Three distinct types of hydrothermal fluids were identified, each with higher temperatures and lower pH, Mg2 + and SO42 -, relative to seawater. Type 1 was consistently more saline than Type 2, and both were more saline than seawater. Type 3 fluids were similar to or slightly depleted in most major ions relative to seawater. End-member calculations of conservative elements indicate that Type 1 and Type 2 fluids are derived from two different sources, most likely 1) a deeper, higher salinity reservoir and 2) a shallower, lower salinity reservoir, respectively, in a layered hydrothermal system. The deeper reservoir records some of the highest end-member Cl concentrations to date, and developed as a result of recirculation of brine fluids with long term loss of steam and volatiles due to past phase separation. No strong evidence for ongoing phase separation is observed. Type 3 fluids are suggested to be mostly influenced by degassing of volatiles and subsequently dissolution of CO2, H2S, and other gases into the aqueous phase. Gibbs energies (ΔGr) of redox reactions that couple potential terminal electron acceptors (O2, NO3-, MnIV, FeIII, SO42 -, S0, CO2,) with potential electron donors (H2, NH4+, Fe2 +, Mn2 +, H2S, CH4) were evaluated at in situ temperatures and compositions for each site and by fluid type. When Gibbs energies of reaction are normalized per kilogram of hydrothermal fluid, sulfur oxidation reactions are the most exergonic, while the oxidation of Fe2 +, NH4+, CH4, and Mn2 + are moderately energy yielding. The energetics calculations indicate that the most robust microbial communities in the Panarea hot springs combine H2S from deep water-rock-gas interactions with O2 that is entrained via seawater mixing to fuel their activities, regardless of site location or fluid type

Loss of STOP Protein Impairs Peripheral Olfactory Neurogenesis

International audienceIn conclusion, STOP protein seems to be involved in the establishment of synapses in the olfactory glomerulus. Our results indicate that the olfactory system of STOP null mice is a well-suited experimental model (1) for the study of the mechanism of action of STOP protein in synaptic function/plasticity and (2) for pathophysiological studies of the mechanisms of altered neuronal connections in schizophrenia