Wednesday, 23 July 2014

What macrophage does what?

Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM, Cialic R, Wu PM, Doykan CE, Lin J, Cotleur AC, Kidd G, Zorlu MM, Sun N, Hu W, Liu L, Lee JC, Taylor SE, Uehlein L, Dixon D, Gu J, Floruta CM, Zhu M, Charo IF, Weiner HL, Ransohoff RM. Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med. 2014 Jul. pii: jem.20132477. [Epub ahead of print]

In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell-mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. We show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an unexpected signature of globally suppressed cellular metabolism at disease onset. Distinguishing tissue-resident macrophages from infiltrating monocytes will point toward new strategies to treat disease and promote repair in diverse inflammatory pathologies in varied organs.
In this study they suggest that blood-derived macrophages that enter the CNS are the cells causing the damage whereas the brain derived macrophages called microglia do the mopping up and clear the debris after this destruction and may promote the repair process.
Targeting the macrophage arm of the immune response can be just as effective as targeting T cell responses, the question is what would the side-effect profile be like?

Using a Tablet to Measure Disability

Rudick RA, Miller D, Bethoux F, Rao SM, Lee JC, Stough D, Reece C, Schindler D, Mamone B, Alberts J.The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool. J Vis Exp. 2014;(88). doi: 10.3791/51318.

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, theMultiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient's home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.

ProfG will like this one as he is a bit of a techie

Rather than explain what it does, why not just click on the link and then see the video of the JOVE website.

It takes about 10.5mins in a few bite size chunks.
The Guys at the Cleveland clinic have developed an ipad-based method for assessing disability. Some of it is is not really high tech but a new way of monitoring old tests, like the peg test and timed walk. However, this creates a digital record

Through technology, much could be done at a distance meaning you don't need to go see a neuro. The sky could be the limit with such a device. Will it change trial design...perhaps.

Now the lead authour has gone to the Dark side, 
Does this mean that ACTRIMS/ECTRIMS gifts will be an ipad for all Neuros? :-) .....Could be worth the investment.