Deletion of TRAAK Potassium Channel Affects Brain Metabolism and Protects against Ischemia

Cerebral stroke is a worldwide leading cause of disability. The two-pore domain K(+) channels identified as background channels are involved in many functions in brain under physiological and pathological conditions. We addressed the hypothesis that TRAAK, a mechano-gated and lipid-sensitive two-pore domain K(+) channel, is involved in the pathophysiology of brain ischemia. We studied the effects of TRAAK deletion on brain morphology and metabolism under physiological conditions, and during temporary focal cerebral ischemia in Traak(-/-) mice using a combination of in vivo magnetic resonance imaging (MRI) techniques and multinuclear magnetic resonance spectroscopy (MRS) methods. We provide the first in vivo evidence establishing a link between TRAAK and neurometabolism. Under physiological conditions, Traak(-/-) mice showed a particular metabolic phenotype characterized by higher levels of taurine and myo-inositol than Traak(+/+) mice. Upon ischemia, Traak(-/-) mice had a smaller infarcted volume, with lower contribution of cellular edema than Traak(+/+) mice. Moreover, brain microcirculation was less damaged, and brain metabolism and pH were preserved. Our results show that expression of TRAAK strongly influences tissue levels of organic osmolytes. Traak(-/-) mice resilience to cellular edema under ischemia appears related to their physiologically high levels of myo-inositol and of taurine, an aminoacid involved in the modulation of mitochondrial activity and cell death. The beneficial effects of TRAAK deletion designate this channel as a promising pharmacological target for the treatment against stroke

Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats

RATIONALE AND OBJECTIVES: The neurotrophic effect of Xaliproden has been followed using sequential cerebral magnetic resonance imaging (MRI) in rats with vincristine-induced brain lesion as a model of Alzheimer disease. METHODS: Nineteen rats received an intraseptal injection of vincristine on day 0, followed by a daily gavage with either the vehicle (Tween-20 1%) (n = 10) or Xaliproden (10 mg/kg) (n = 9). Eight sham-operated controls received a daily gavage with either the vehicle (n = 4) or Xaliproden (n = 4). Brain MR imaging was performed at 4.7 T on a Biospec 47/30 MR system before surgery then 3, 7, 10, and 14 days after surgery. RESULTS: At day 3 following vincristine injection, an increase in MR signal intensity in the septum was observed on T2-weighted images. This increase was maximal at day 10, and remained stable until day 14. Daily treatment with Xaliproden delayed the appearance of hypersignals until day 7 and reduced by Ca. 50% the magnitude of the increase in signal intensity from day 10. No changes were observed in the hippocampus. CONCLUSION: Quantitative MRI objectifies noninvasively the neuroprotective effect of Xaliproden on rat brain anatomy

Diffusion-weighted imaging in normal fetal brain maturation

Diffusion-weighted imaging (DWI) provides information about tissue maturation not seen on conventional magnetic resonance imaging. The aim of this study is to analyze the evolution over time of the apparent diffusion coefficient (ADC) of normal fetal brain in utero. DWI was performed on 78 fetuses, ranging from 23 to 37 gestational weeks (GW). All children showed at follow-up a normal neurological evaluation. ADC values were obtained in the deep white matter (DWM) of the centrum semiovale, the frontal, parietal, occipital and temporal lobe, in the cerebellar hemisphere, the brainstem, the basal ganglia (BG) and the thalamus. Mean ADC values in supratentorial DWM areas (1.68 ± 0.05mm2/s) were higher compared with the cerebellar hemisphere (1.25 ± 0.06mm2/s) and lowest in the pons (1.11 ± 0.05mm2/s). Thalamus and BG showed intermediate values (1.25 ± 0.04mm2/s). Brainstem, cerebellar hemisphere and thalamus showed a linear negative correlation with gestational age. Supratentorial areas revealed an increase in ADC values, followed by a decrease after the 30th GW. This study provides a normative data set that allows insights in the normal fetal brain maturation in utero, which has not yet been observed in previous studies on premature babie

Development of a reverse genetics system for Toscana virus (lineage A)

Toscana virus (TOSV) is a Phlebovirus in the Phenuiviridae family, order Bunyavirales, found in the countries surrounding the Mediterranean. TOSV is an important cause of seasonal acute meningitis and encephalitis within its range. Here, we determined the full sequence of the TOSV strain 1500590, a lineage A virus obtained from an infected patient (Marseille, 2007) and used this in combination with other sequence information to construct functional cDNA plasmids encoding the viral L, M, and S antigenomic sequences under the control of the T7 RNA promoter to recover recombinant viruses. Importantly, resequencing identified two single nucleotide changes to a TOSV reference genome, which, when corrected, restored functionality to the polymerase L and made it possible to recover infectious recombinant TOSV (rTOSV) from cDNA, as well as establish a minigenome system. Using reverse genetics, we produced an NSs-deletant rTOSV and also obtained viruses expressing reporter genes instead of NSs. The availability of such a system assists investigating questions that require genetic manipulation of the viral genome, such as investigations into replication and tropism, and beyond these fundamental aspects, also the development of novel vaccine design strategies

Main clinical features in patients at their first psychiatric admission to Italian acute hospital psychiatric wards. The PERSEO study

BACKGROUND: Few data are available on subjects presenting to acute wards for the first time with psychotic symptoms. The aims of this paper are (i) to describe the epidemiological and clinical characteristics of patients at their first psychiatric admission (FPA), including socio-demographic features, risk factors, life habits, modalities of onset, psychiatric diagnoses and treatments before admission; (ii) to assess the aggressive behavior and the clinical management of FPA patients in Italian acute hospital psychiatric wards, called SPDCs (Servizio Psichiatrico Diagnosi e Cura = psychiatric service for diagnosis and management). METHOD: Cross-sectional observational multi-center study involving 62 Italian SPDCs (PERSEO – Psychiatric EmeRgency Study and EpidemiOlogy). RESULTS: 253 FPA aged <= 40 were identified among 2521 patients admitted to Italian SPDCs over the 5-month study period. About half of FPA patients showed an aggressive behavior as defined by a Modified Overt Aggression Scale (MOAS) score greater than 0 Vs 46% of non-FPA patients (p = 0.3651). The most common was verbal aggression, while about 20% of FPA patients actually engaged in physical aggression against other people. 74% of FPA patients had no diagnosis at admission, while 40% had received a previous psychopharmacological treatment, mainly benzodiazepines and antidepressants. During SPDC stay, diagnosis was established in 96% of FPA patients and a pharmacological therapy was prescribed to 95% of them, mainly benzodiazepines, antipsychotics and mood stabilizers. CONCLUSION: Subjects presenting at their first psychiatric ward admission have often not undergone previous adequate psychiatric assessment and diagnostic procedures. The first hospital admission allows diagnosis and psychopharmacological treatment to be established. In our population, aggressive behaviors were rather frequent, although most commonly verbal. Psychiatric symptoms, as evaluated by psychiatrists and patients, improved significantly from admission to discharge both for FPA and non-FPA patients

Interictal Functional Connectivity of Human Epileptic Networks Assessed by Intracerebral EEG and BOLD Signal Fluctuations

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE

One Health: The global challenge of epidemic and endemic leishmaniasis

'One Health' proposes the unification of medical and veterinary sciences with the establishment of collaborative ventures in clinical care, surveillance and control of cross-species disease, education, and research into disease pathogenesis, diagnosis, therapy and vaccination. The concept encompasses the human population, domestic animals and wildlife, and the impact that environmental changes ('environmental health') such as global warming will have on these populations. Visceral leishmaniasis is a perfect example of a small companion animal disease for which prevention and control might abolish or decrease the suffering of canine and human patients, and which aligns well with the One Health approach. In this review we discuss how surveillance for leishmaniases is undertaken globally through the control of anthroponootic visceral leishmaniasis (AVL) and zoonotic visceral leishmaniasis (ZVL). The ZVL epidemic has been managed to date by the culling of infected dogs, treatment of human cases and control of the sandfly vector by insecticidal treatment of human homes and the canine reservoir. Recently, preventive vaccination of dogs in Brazil has led to reduction in the incidence of the canine and human disease. Vaccination permits greater dog owner compliance with control measures than a culling programme. Another advance in disease control in Africa is provided by a surveillance programme that combines remote satellite sensing, ecological modelling, vector surveillance and geo-spatial mapping of the distribution of vectors and of the animal-to-animal or animal-to-human pathogen transmission. This coordinated programme generates advisory notices and alerts on emerging infectious disease outbreaks that may impede or avoid the spreading of visceral leishmaniasis to new areas of the planet as a consequence of global warming

Application of reverse‐DEPT polarization transfer pulse sequence to study the metabolism of carbon‐13‐labeled substrates in perfused organs by 1H NMR Spectroscopy

Metabolism of C‐enriched metabolites can be advantageously studied by reverse‐polarization transfer methods. In this work an improved reverse‐DEPT sequence has been applied for the first time on perfused organs in a 20‐mm probe. The metabolic fate of 99% enriched [ 2‐C] acetate perfused in excised rat liver and heart has been documented. © 1990 Academic Press, Inc