Oxidative stress in rat brain during experimental status epilepticus: effect of antioxidants.

Antioxidants have been proposed as a treatment for diseases of the central nervous system. However, few studies actually studied their effects in the brain. To test central actions of antioxidants, we used the lithium-pilocarpine (Li-Pilo) model of status epilepticus (SE) in the rat in which seizures are accompanied by significant oxidative stress. We used in vivo microdialysis to determine isoprostane levels during SE in real time and brain homogenates for other measures of oxidative stress. Six different antioxidants were tested in acute and preventive experiments (vitamin C, vitamin E, ebselen, resveratrol, n-tert-butyl-α-phenylnitrone and coenzyme Q10). None of the antioxidants had an effect when given acutely during SE. In contrast, when antioxidants were given for 3 days prior to seizure induction, vitamins C and E reduced isoprostane formation by 58% and 65%, respectively. Pretreatment with the other antioxidants was ineffective. In brain homogenates prepared after 90 min of seizures, SE decreased the ratio of reduced vs. oxidized glutathione (GSH/GSSG ratio) from 60.8 to 7.50 and caused a twofold increase of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and protein carbonyls. Pretreatment with vitamin C or vitamin E mitigated these effects and increased the GSH/GSSG ratio to 23.9 and 28.3, respectively. Again, the other antioxidants were not effective. We conclude that preventive treatment with vitamin C or vitamin E ameliorates seizure-induced oxidative damage in the brain. Several well-studied antioxidants were inactive, possibly due to limited brain permeability or a lack of chain-breaking antioxidant activity in hydrophilic compounds.

ß-Hydroxybutyrate Improves Mitochondrial Function After Transient Ischemia in the Mouse.

ß-Hydroxybutyrate (BHB) is a ketone body formed in high amounts during lipolysis and fasting. Ketone bodies and the ketogenic diet were suggested as neuroprotective agents in neurodegenerative disease. In the present work, we induced transient ischemia in mouse brain by unilaterally occluding the middle cerebral artery for 90 min. BHB (30 mg/kg), given immediately after reperfusion, significantly improved the neurological score determined after 24 h. In isolated mitochondria from mouse brain, oxygen consumption by the complexes I, II and IV was reduced immediately after ischemia but recovered slowly over 1 week. The single acute BHB administration after reperfusion improved complex I and II activity after 24 h while no significant effects were seen at later time points. After 24 h, plasma and brain BHB concentrations were strongly increased while mitochondrial intermediates (citrate, succinate) were unchanged in brain tissue. Our data suggest that a single administration of BHB may improve mitochondrial respiration for 1-2 days but not for later time points. Endogenous BHB formation seems to complement the effects of exogenous BHB administration.

Effects of Magnesium Orotate, Benfotiamine and a Combination of Vitamins on Mitochondrial and Cholinergic Function in the TgF344-AD Rat Model of Alzheimer's Disease.

Glucose hypometabolism, mitochondrial dysfunction, and cholinergic deficits have been reported in early stages of Alzheimer's disease (AD). Here, we examine these parameters in TgF344-AD rats, an Alzheimer model that carries amyloid precursor protein and presenilin-1 mutations, and of wild type F344 rats. In mitochondria isolated from rat hippocampi, we found reductions of complex I and oxidative phosphorylation in transgenic rats. Further impairments, also of complex II, were observed in aged (wild-type and transgenic) rats. Treatment with a "cocktail" containing magnesium orotate, benfotiamine, folic acid, cyanocobalamin, and cholecalciferol did not affect mitochondrial activities in wild-type rats but restored diminished activities in transgenic rats to wild-type levels. Glucose, lactate, and pyruvate levels were unchanged by age, genetic background, or treatment. Using microdialysis, we also investigated extracellular concentrations of acetylcholine that were strongly reduced in transgenic animals. Again, ACh levels in wild-type rats did not change upon treatment with nutrients, whereas the cocktail increased hippocampal acetylcholine levels under physiological stimulation. We conclude that TgF344-AD rats display a distinct mitochondrial and cholinergic dysfunction not unlike the findings in patients suffering from AD. This dysfunction can be partially corrected by the application of the "cocktail" which is particularly active in aged rats. We suggest that the TgF344-AD rat is a promising model to further investigate mitochondrial and cholinergic dysfunction and potential treatment approaches for AD.

Malaria in Burkina Faso (West Africa) during the twenty-first century.

Temperature and rainfall predicted for the twenty-first century by global coupled models as reported by IPCC, (2014a, and b) were obtained regionally for Burkina Faso and through the Paluclim project, 2011-2014. One of the goals of this project was to assess the upcoming evolution of malaria transmission dynamics. From an impact model on malaria risk linked to climate variability, temperature and rainfall indices were derived. Malaria transmission dynamics were then predicted using the derived temperature and rainfall for the twenty-first century. Similar to the historical evidence of rainfall being an important factor for regulating the seasonal density of malaria vectors, this study also reports a definitive link between low-frequency rainfall variability and malaria in the region under the influence of the Atlantic Multidecadal Oscillation (AMO). This finding can be used by local stakeholders involved with the geography-based population health planning. Moreover, the predicted increase in temperature during the twenty-first century suggests a reduction of larvae survival in Burkina Faso and thus the malaria risk. More generally, the temperature increase could become a new limiting factor for malaria transmission dynamics in the Sahel Region (as reported by Mordecai et al. (2013).

Climate impact on malaria in northern Burkina Faso.

The Paluclim project managed by the French Centre National d'Etudes Spatiales (CNES) found that total rainfall for a 3-month period is a confounding factor for the density of malaria vectors in the region of Nouna in the Sahel administrative territory of northern Burkina Faso. Following the models introduced in 1999 by Craig et al. and in 2003 by Tanser et al., a climate impact model for malaria risk (using different climate indices) was created. Several predictions of this risk at different temporal scales (i.e. seasonal, inter-annual and low-frequency) were assessed using this climate model. The main result of this investigation was the discovery of a significant link between malaria risk and low-frequency rainfall variability related to the Atlantic Multi-decadal Oscillation (AMO). This result is critical for the health information systems in this region. Knowledge of the AMO phases would help local authorities to organise preparedness and prevention of malaria, which is of particular importance in the climate change context.

Operational Mapping of Soil Moisture Using Synthetic Aperture Radar Data: Application to the Touch Basin (France).

Soil moisture is a key parameter in different environmental applications, suchas hydrology and natural risk assessment. In this paper, surface soil moisture mappingwas carried out over a basin in France using satellite synthetic aperture radar (SAR)images acquired in 2006 and 2007 by C-band (5.3 GHz) sensors. The comparisonbetween soil moisture estimated from SAR data and in situ measurements shows goodagreement, with a mapping accuracy better than 3%. This result shows that themonitoring of soil moisture from SAR images is possible in operational phase. Moreover,moistures simulated by the operational Météo-France ISBA soil-vegetation-atmospheretransfer model in the SIM-Safran-ISBA-Modcou chain were compared to radar moistureestimates to validate its pertinence. The difference between ISBA simulations and radarestimates fluctuates between 0.4 and 10% (RMSE). The comparison between ISBA andgravimetric measurements of the 12 March 2007 shows a RMSE of about 6%. Generally,these results are very encouraging. Results show also that the soil moisture estimatedfrom SAR images is not correlated with the textural units defined in the European Soil Geographical Database (SGDBE) at 1:1000000 scale. However, dependence was observed between texture maps and ISBA moisture. This dependence is induced by the use of the texture map as an input parameter in the ISBA model. Even if this parameter is very important for soil moisture estimations, radar results shown that the textural map scale at 1:1000000 is not appropriate to differentiate moistures zones.