ExperimentalNeuropathology

 

We established the Experimental Neuropathology Laboratory, an independent research laboratory, in 2000. The focus of the work of our laboratory is to identify how inflammation contributes to the outcome of acute and chronic brain injury or infection.


Inflammation, the response of the host to a variety of injuries, is usually desirable and beneficial. However, inflammation can be inappropriate or excessive, leading to tissue destruction. There is now considerable evidence to support the idea that inflammation contributes not only to the archetypal inflammatory disease of the brain, multiple sclerosis, but also to acute neurological diseases, such as stroke and head trauma, and to chronic neurodegenerative diseases, such as Alzheimer’s disease, prion disease, and HIV-related dementia. For all of these neuropathologies, in which inflammation is undoubtedly an important factor, there is considerable debate as to how the host response contributes to outcome and at what time in the pathogenesis it is most important. Our results indicate that where inflammation contributes to the disease progression in neurodegenerative disease, it does so in a punctuate manner (on-off) as a result of systemic events that activate ‘primed’ microglia into a destructive phenotype. We now have evidence that this happens as a consequence of chemokine production by the liver as part of the acute phase response. Further information about the role of inflammation in the CNS and the interaction between brain pathology and the function of the immune system can be found in a recent set of reviews published in MCN.




Recent news

We have previously shown that it is possible to discriminate between different inflammatory lesions in the central nervous system in rats through analysis of urine samples, using a combination of magnetic resonance spectroscopy and partial least squares discriminate analysis. Based on these data, we sought to discover whether this approach could be used to differentiate between sequential disease states in a relapsing-remitting animal model of Multiple Sclerosis (MS) and in Multiple Sclerosis.  We have been able to distinguish Cr-EAE mice from control mice, treated with complete Freund’s adjuvant alone, at all time-points. Key metabolites that underpin these models include fatty acids, taurine, and citrate. Most importantly, we have also shown that we can use this technique to separate individuals with MS with 100% sensitivity and specificity. Furthermore, we can also stage individuals with MS with very high sensitivity and specificity.  This could lead to a non-invasive diagnostic test for staging multiple sclerosis in people. Furthermore, we have also been applying this approach to other pathologies, including HIV and brain metastasis, and found that we can usefully distinguish between different disease states.

See some of our recent metabolomics publications here:

NMR-Based Metabolomics Separates the Distinct Stages of Disease in a Chronic Relapsing Model of Multiple Sclerosis. Dickens AM, Larkin JR, Davis BG, Griffin JL, Claridge TD, Sibson NR, Anthony DC. J Neuroimmune Pharmacol. 2015 Jul 9. [Epub ahead of print]

Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients. Dickens AM, Anthony DC, Deutsch R, Mielke MM, Claridge TD, Grant I, Franklin D, Rosario D, Marcotte T, Letendre S, McArthur JC, Haughey NJ. AIDS. 2015 Mar 13;29(5):559-69. doi: 10.1097/QAD.0000000000000580.

A type 2 biomarker separates relapsing-remitting from secondary progressive multiple sclerosis. Dickens AM, Larkin JR, Griffin JL, Cavey A, Matthews L, Turner MR, Wilcock GK, Davis BG, Claridge TD, Palace J, Anthony DC, Sibson NR. Neurology. 2014 Oct 21;83(17):1492-9. doi: 10.1212/WNL.0000000000000905. Epub 2014 Sep 24.





 

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  1. 1.Labelled Microparticles on BV2 cells

  2. 2.Department of Pharmacology

  3. 3.The Anthony Lab

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