via PLoS ONE Alerts: Neurological Disorders by Louise Robinson et al. on 5/25/12

by Louise Robinson, Michael D. Spencer, Lindsay D. G. Thomson, Andrew C. Stanfield, David G. C. Owens, Jeremy Hall, Eve C. Johnstone

Aims

We aimed to evaluate this tool in Scottish prisoners by comparing scores with standard measures of autistic traits (Autism Quotient (AQ)), neurodevelopmental history (Asperger Syndrome (and High-Functioning Autism) Diagnostic Interview (ASDI)), and social cognition (Ekman 60 Faces test).

Methods

Prison officers across all 12 publicly-run closed prisons in Scotland assessed convicted prisoners using the screening tool. This sample included male and female prisoners and both adult and young offenders. Prisoners with high scores, along with an equal number of age and sex-matched controls, were invited to take part in interviews. Prisoners' relatives were contacted to complete a neurodevelopmental assessment.

Results

2458 prisoners were screened using the tool, and 4% scored above the cut-off. 126 prisoners were further assessed using standardised measures. 7 of those 126 assessed scored 32 or above (cut-off) on the AQ. 44 interviews were completed with prisoners' relatives, no prisoner reached the cut-off score on the ASDI. Scores on the screening tool correlated significantly with AQ and ASDI scores, and not with the Ekman 60 Faces Test or IQ. Sensitivity was 28.6% and specificity 75.6%; AUC was 59.6%.

Conclusions

Although this screening tool measures autistic traits in this population, sensitivity for scores of 32 or above on the AQ is poor. We consider that this limits its usefulness and do not recommend that the tool is routinely used to screen for ASDs in prisons.

via PLoS ONE Alerts: Neurological Disorders by Siddharth Nanguneri et al. on 5/25/12

by Siddharth Nanguneri, Benjamin Flottmann, Heinz Horstmann, Mike Heilemann, Thomas Kuner

Three-dimensional fluorescence imaging of thick tissue samples with near-molecular resolution remains a fundamental challenge in the life sciences. To tackle this, we developed tomoSTORM, an approach combining single-molecule localization-based super-resolution microscopy with array tomography of structurally intact brain tissue. Consecutive sections organized in a ribbon were serially imaged with a lateral resolution of 28 nm and an axial resolution of 40 nm in tissue volumes of up to 50 µm×50 µm×2.5 µm. Using targeted expression of membrane bound (m)GFP and immunohistochemistry at the calyx of Held, a model synapse for central glutamatergic neurotransmission, we delineated the course of the membrane and fine-structure of mitochondria. This method allows multiplexed super-resolution imaging in large tissue volumes with a resolution three orders of magnitude better than confocal microscopy.

via PLoS ONE Alerts: Neurological Disorders by Nghia Ho Dang Trung et al. on 5/25/12

by Nghia Ho Dang Trung, Tu Le Thi Phuong, Marcel Wolbers, Hoang Nguyen Van Minh, Vinh Nguyen Thanh, Minh Pham Van, Nga Tran Vu Thieu, Tan Le Van, Diep To Song, Phuong Le Thi, Thao Nguyen Thi Phuong, Cong Bui Van, Vu Tang, Tuan Hoang Ngoc Anh, Dong Nguyen, Tien Phan Trung, Lien Nguyen Thi Nam, Hao Tran Kiem, Tam Nguyen Thi Thanh, James Campbell, Maxine Caws, Jeremy Day, Menno D. de Jong, Chau Nguyen Van Vinh, H. Rogier Van Doorn, Hien Tran Tinh, Jeremy Farrar, Constance Schultsz, the VIZIONS CNS Infection Network

Background

Infectious diseases of the central nervous system (CNS) remain common and life-threatening, especially in developing countries. Knowledge of the aetiological agents responsible for these infections is essential to guide empiric therapy and develop a rational public health policy. To date most data has come from patients admitted to tertiary referral hospitals in Asia and there is limited aetiological data at the provincial hospital level where most patients are seen.

Methods

We conducted a prospective Provincial Hospital-based descriptive surveillance study in adults and children at thirteen hospitals in central and southern Viet Nam between August 2007– April 2010. The pathogens of CNS infection were confirmed in CSF and blood samples by using classical microbiology, molecular diagnostics and serology.

Results

We recruited 1241 patients with clinically suspected infection of the CNS. An aetiological agent was identified in 640/1241 (52%) of the patients. The most common pathogens were Streptococcus suis serotype 2 in patients older than 14 years of age (147/617, 24%) and Japanese encephalitis virus in patients less than 14 years old (142/624, 23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and 11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children.

Conclusions

Zoonotic bacterial and viral pathogens are the most common causes of CNS infection in adults and children in Viet Nam.

via PLoS ONE Alerts: Neurological Disorders by Sonia Gandhi et al. on 5/25/12

by Sonia Gandhi, Annika Vaarmann, Zhi Yao, Michael R. Duchen, Nicholas W. Wood, Andrey Y. Abramov

Background

Parkinson's disease is a common neurodegenerative disease characterised by progressive loss of dopaminergic neurons, leading to dopamine depletion in the striatum. Mutations in the PINK1 gene cause an autosomal recessive form of Parkinson's disease. Loss of PINK1 function causes mitochondrial dysfunction, increased reactive oxygen species production and calcium dysregulation, which increases susceptibility to neuronal death in Parkinson's disease. The basis of neuronal vulnerability to dopamine in Parkinson's disease is not well understood.

Methodology

We investigated the mechanism of dopamine induced cell death in transgenic PINK1 knockout mouse neurons. We show that dopamine results in mitochondrial depolarisation caused by mitochondrial permeability transition pore (mPTP) opening. Dopamine-induced mPTP opening is dependent on a complex of reactive oxygen species production and calcium signalling. Dopamine-induced mPTP opening, and dopamine-induced cell death, could be prevented by inhibition of reactive oxygen species production, by provision of respiratory chain substrates, and by alteration in calcium signalling.

Conclusions

These data demonstrate the mechanism of dopamine toxicity in PINK1 deficient neurons, and suggest potential therapeutic strategies for neuroprotection in Parkinson's disease.

via PLoS ONE Alerts: Neurological Disorders by Éva Ruisanchez et al. on 5/25/12

by Éva Ruisanchez, Attila Cselenyák, Rege Sugárka Papp, Tamás Németh, Krisztina Káldi, Péter Sándor, Zoltán Benyó

Background

Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect.

Methodology/Principal Findings

Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1–13) and DYN-A (1–17) but not DYN-A (1–8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K+, were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 µM of DYN-A (1–13) and DYN-A (1–17), respectively. The vasoconstrictor effects of DYN-A (1–13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of Gi/o-protein mediated signaling by pertussis toxin. Finally, des-Tyr1 DYN-A (2–13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 µM, which effects were resistant to NORBI.

Conclusion/Significance

DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric Gi/o-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors.

via PLoS ONE Alerts: Neurological Disorders by Lei Wang et al. on 5/25/12

by Lei Wang, Heng Guo, Xiao Yu, Shouyan Wang, Canhua Xu, Feng Fu, Xiaorong Jing, Hua Zhang, Xiuzhen Dong

Background

A responsive electrical stimulation pattern based on our recently developed novel seizure prediction method was designed to suppress the penicillin-induced epileptic seizures.

Methodology

Seizures were induced by Penicillin injection at rat cortex. A responsive electrical stimulation system was triggered prior to seizures predicted with phase synchronisation. Rats with induced seizures were stimulated by the electrical pulses at a responsive or 1 Hz periodic pattern of an open system. The effectiveness of stimulation on seizures suppression was assessed by measuring the average number and duration of seizures per hour.

Results

The prediction algorithm reliably identified seizures in real time and triggered the responsive stimulation. This type of electrical stimulation dramatically suppressed seizure activity and the performance was better than the open stimulation system with fewer and shorter seizures.

Conclusions

A responsive electrical stimulation system triggered by the phase synchronisation prediction is able to significantly suppress seizures.

Significance

Responsive electrical stimulation could achieve superior treatment performance and reduce power consumption and side effects.

via PLoS ONE Alerts: Neurological Disorders by Virginie F. Labrousse et al. on 5/25/12

by Virginie F. Labrousse, Agnès Nadjar, Corinne Joffre, Laurence Costes, Agnès Aubert, Stéphane Grégoire, Lionel Bretillon, Sophie Layé

Regular consumption of food enriched in omega3 polyunsaturated fatty acids (ω3 PUFAs) has been shown to reduce risk of cognitive decline in elderly, and possibly development of Alzheimer's disease. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are the most likely active components of ω3-rich PUFAs diets in the brain. We therefore hypothesized that exposing mice to a DHA and EPA enriched diet may reduce neuroinflammation and protect against memory impairment in aged mice. For this purpose, mice were exposed to a control diet throughout life and were further submitted to a diet enriched in EPA and DHA during 2 additional months. Cytokine expression together with a thorough analysis of astrocytes morphology assessed by a 3D reconstruction was measured in the hippocampus of young (3-month-old) and aged (22-month-old) mice. In addition, the effects of EPA and DHA on spatial memory and associated Fos activation in the hippocampus were assessed. We showed that a 2-month EPA/DHA treatment increased these long-chain ω3 PUFAs in the brain, prevented cytokines expression and astrocytes morphology changes in the hippocampus and restored spatial memory deficits and Fos-associated activation in the hippocampus of aged mice. Collectively, these data indicated that diet-induced accumulation of EPA and DHA in the brain protects against neuroinflammation and cognitive impairment linked to aging, further reinforcing the idea that increased EPA and DHA intake may provide protection to the brain of aged subjects.

via PLoS ONE Alerts: Neurological Disorders by Xin Wang et al. on 5/25/12

by Xin Wang, Zunji Ke, Gang Chen, Mei Xu, Kimberly A. Bower, Jacqueline A. Frank, Zhuo Zhang, Xianglin Shi, Jia Luo

It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47phox and p67phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and membrane translocation of p47phox and p67phox, which were prerequisites for NOX assembly and activation. Knocking down p47phox with the small interfering RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate ethanol-mediated oxidative damage, which is indicated by a decrease in protein oxidation and lipid peroxidation. Ethanol activated cell division cycle 42 (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol-induced NOX activation and ROS generation. These results suggest that Cdc42-dependent NOX activation mediates ethanol-induced oxidative damages to neurons.

via PLoS ONE Alerts: Neurological Disorders by Rongfeng Qi et al. on 5/25/12

by Rongfeng Qi, Long Jiang Zhang, Qiang Xu, Jianhui Zhong, Shengyong Wu, Zhiqiang Zhang, Wei Liao, Ling Ni, Zongjun Zhang, Huafu Chen, Yuan Zhong, Qing Jiao, Xingjiang Wu, Xinxin Fan, Yijun Liu, Guangming Lu

Background

Minimal hepatic encephalopathy (MHE) is a neuro-cognitive dysfunction characterized by impairment in attention, vigilance and integrative functions, while the sensorimotor function was often unaffected. Little is known, so far, about the exact neuro-pathophysiological mechanisms of aberrant cognition function in this disease.

Methodology/Principal Findings

To investigate how the brain function is changed in MHE, we applied a resting-state fMRI approach with independent component analysis (ICA) to assess the differences of resting-state networks (RSNs) between MHE patients and healthy controls. Fourteen MHE patients and 14 age-and sex-matched healthy subjects underwent resting-state fMRI scans. ICA was used to identify six RSNs [dorsal attention network (DAN), default mode network (DMN), visual network (VN), auditory network (AN), sensorimotor network (SMN), self-referential network (SRN)] in each subject. Group maps of each RSN were compared between the MHE and healthy control groups. Pearson correlation analysis was performed between the RSNs functional connectivity (FC) and venous blood ammonia levels, and neuropsychological tests scores for all patients. Compared with the healthy controls, MHE patients showed significantly decreased FC in DAN, both decreased and increased FC in DMN, AN and VN. No significant differences were found in SRN and SMN between two groups. A relationship between FC and blood ammonia levels/neuropsychological tests scores were found in specific regions of RSNs, including middle and medial frontal gyrus, inferior parietal lobule, as well as anterior and posterior cingulate cortex/precuneus.

Conclusions/Significance

MHE patients have selective impairments of RSNs intrinsic functional connectivity, with aberrant functional connectivity in DAN, DMN, VN, AN, and spared SMN and SRN. Our fMRI study might supply a novel way to understand the neuropathophysiological mechanism of cognition function changes in MHE.