Immunologic privilege in the central nervous system and the blood-brain barrier

The brain is in many ways an immunologically and pharmacologically privileged site. The blood-brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.

Competition for neuronal resources: how hallucinations make themselves heard

BACKGROUND: Hallucinations are perceptions in the absence of a corresponding external sensory stimulus. However, during auditory verbal hallucinations, activation of the primary auditory cortex has been described. AIMS: The objective of this study was to investigate whether this activation of the auditory cortex contributes essentially to the character of hallucinations and attributes them to alien sources, or whether the auditory activation is a sign of increased general auditory attention to external sounds. METHOD: The responsiveness of the auditory cortex was investigated by auditory evoked potentials (N100) during the simultaneous occurrence of hallucinations and external stimuli. Evoked potentials were computed separately for periods with and without hallucinations; N100 power, topography and brain electrical sources were analysed. RESULTS: Hallucinations lowered the N100 amplitudes and changed the topography, presumably due to a reduced left temporal responsivity. CONCLUSIONS: This finding indicates competition between auditory stimuli and hallucinations for physiological resources in the primary auditory cortex. The abnormal activation of the primary auditory cortex may thus be a constituent of auditory hallucinations.

Retrofitting boreholes contaminated with iron in rural Uganda

During my Peace Corps service as a community health liaison in rural Uganda I noticed that many improved water wells in our area had been abandoned. The communities described the water in these wells as being reddish in color, having a foul taste and odor, discoloring clothes and food, and not able to produce lather for washing. Personal investigations and an initial literature search suggested that the primary contaminant was iron. The water in these wells had a low pH and a rusty metallic smell. The water produced early in the morning appeared very red but the water became more transparent as pumping continued. The iron components of many of these wells experienced accelerated corrosion resulting in frequent pump failure. This rapid corrosion coupled with the timing of the onset of iron contamination (months to years after these wells were completed) suggests that the most likely cause of the poor quality water was iron related bacteria and/or sulphate reducing bacteria. This report describes a remedy for iron contamination employed at 5 wells. The remedy involved disinfecting the wells with chlorine and replacing iron pump components with plastic and stainless steel. Iron concentrations in the wells were less than 1 mg/L when the wells were drilled but ranged from 2.5 to 40 mg/L prior to the remedy. After the remedy was applied, the total iron concentrations returned to levels below 1 mg/L. The presence of iron related bacteria was measured in all of these wells using Biological Activity Reaction Tests. Although IRB are still present in all the wells, the dissolved iron concentrations remain less than 1 mg/L. This remedy is practical for rural areas because the work can be performed with only hand tools and costs less than US $850. Because the source of iron contamination is removed in this approach, substantial follow-up maintenance is not necessary.

Strategies to advance translational research into brain barriers

There is a paucity of therapies for most neurological disorders--from rare lysosomal storage diseases to major public health concerns such as stroke and Alzheimer's disease. Advances in the targeting of drugs to the CNS are essential for the future success of neurotherapeutics; however, the delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by the blood-brain barrier, the blood-CSF barrier, or other specialised CNS barriers. These brain barriers are now recognised as a major obstacle to the treatment of most brain disorders. The challenge to deliver therapies to the CNS is formidable, and the solution will require concerted international efforts among academia, government, and industry. At a recent meeting of expert panels, essential and high-priority recommendations to propel brain barrier research forward in six topical areas were developed and these recommendations are presented here.

Treatment Technology Validation for Water Softening Technology

MT Hard Water of Montana Tech of the University of Montana submits Task 3: Treatment Technology Validation for Water Softening Technology as an entry into the 2012 WERC Environmental Design Contest. Currently, there are several commercially available technologies that treat water hardness. The objective of this project is to develop a strategy to evaluate and validate different water hardness treatment technologies. MT Hard Water (MTHW) has studied several technologies including: electromagnetic water treatment, ion exchange, and reverse osmosis. For validation purposes, an electromagnetic water treatment system (ScaleRID) was selected according to the WERC task description.

Siliceous Sponge Spicules of the Quadrant Formation from Montana.

A sponge spicule is a siliceous or calcareous individual or group of rays which form a framework for the sponge. Sponge spicules are very delicate and easily broken. The methods used in obtaining micro-fossils vary considerably with the type of material from which they are to be recovered and the frailness of the fossil obtained.

A Preliminary Investigation of Chromite

The purpose of this thesis was to study the effects of cryolite and a mixture of cryolite and aluminum oxide on a chromite concentrate with special reference to the ability to break the bond between the ferrous iron and chromic oxide in the chromite.

Statistical analysis of multichannel scalp field data

High density spatial and temporal sampling of EEG data enhances the quality of results of electrophysiological experiments. Because EEG sources typically produce widespread electric fields (see Chapter 3) and operate at frequencies well below the sampling rate, increasing the number of electrodes and time samples will not necessarily increase the number of observed processes, but mainly increase the accuracy of the representation of these processes. This is namely the case when inverse solutions are computed. As a consequence, increasing the sampling in space and time increases the redundancy of the data (in space, because electrodes are correlated due to volume conduction, and time, because neighboring time points are correlated), while the degrees of freedom of the data change only little. This has to be taken into account when statistical inferences are to be made from the data. However, in many ERP studies, the intrinsic correlation structure of the data has been disregarded. Often, some electrodes or groups of electrodes are a priori selected as the analysis entity and considered as repeated (within subject) measures that are analyzed using standard univariate statistics. The increased spatial resolution obtained with more electrodes is thus poorly represented by the resulting statistics. In addition, the assumptions made (e.g. in terms of what constitutes a repeated measure) are not supported by what we know about the properties of EEG data. From the point of view of physics (see Chapter 3), the natural “atomic” analysis entity of EEG and ERP data is the scalp electric field