Volume 1

The revision of the EU Directive on the protection of animals used for scientific purposes / House of Lords. European Union Committee.

  • Great Britain. Parliament. House of Lords. European Union Committee
Date:
2009
Catalogue details

Licence: Open Government Licence

Credit: The revision of the EU Directive on the protection of animals used for scientific purposes / House of Lords. European Union Committee. Source: Wellcome Collection.

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    a It is essential to reappraise whether valuable, functional data about the immunology of multiple sclerosis can better be obtained from studies of human patient T-cell responses. The advantage of this is that, in what is a rather heterogeneous and poorly understood disease, one avoids any of the prior assumptions as to mechanisms that necessarily constrain the animal models. Recent advances in molecular understanding and immunological reagents mean that one can now gain considerable insight into MS-related T cell immune processes from ex vivo analysis [4, 5]. This can encompass analysis of specificity, tetramer binding, clonality, cytokine profile, markers of in vivo replicative history and expression of cell-surface antigens to allow sub-setting of responding human cells into recent memory, chronically stimulated, effector memory and senescent effector T cells. Furthermore, it is increasingly possible to evaluate the role of particular molecules in culture through the use of siRNA knockdown approaches [6]. A shift to human in vitro studies for studying multiple sclerosis disease mechanisms also offers a major advantage in research costs. REFERENCES 1. Rivers T M, Sprunt D H, Berry G P (1933) Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J Exp Med 58:39-53. 2. Gold R, Linington C, Lassmann H (2006) Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain. 129:1953-1971. 3. ‘t Hart B A, Bauer J, Brok H P and Amor S (2005) Non-human primate models of experimental autoimmune encephalomyelitis: Variations on a theme. J Neuroimmunol. 168:1—12. 4. Davies S, Nicholson T, Laura M, Giovannoni G and Altmann D M (2005) Spread of T lymphocyte responses to myelin epitopes with duration of multiple sclerosis. J Neuropath Exp Neurol 64:371. 5. Bielekova B, Sung M, Kadom N, Simon R, McFarland H, Martin R (2004) Expansion and Functional Relevance of High-Avidity Myelin-Specific CD4+ T Cells in Multiple Sclerosis. J Immunol 172:3893—3904. 6. Hafler D A (2004) Multiple sclerosis. J Clin Invest 113:788—794. AS. Human brain networks: Computational frameworks to analyse human brain networks and their breakdown in disease using diffusion tensor imaging Dr Heidi Johansen-Berg and Dr Tim Behrens from Oxford University have a grant from the Dr Hadwen Trust to develop computational approaches for analysing human brain networks and their breakdown in disease. There are several neurological and psychiatric disorders in which connections between deep brain structures and cortical regions are damaged or disrupted. They include schizophrenia, chronic pain, and movement disorders such as Parkinson’s disease. Detailed knowledge of human subcortical-cortical brain circuitry is therefore crucial to understanding and treating these disorders. At present much knowledge of brain connectivity comes from inferences based on invasive tracer studies in animals, including rodents, cats and monkeys. Recent developments in the field of non-invasive diffusion tensor magnetic resonance imaging (DTMRI) allow tracing of fibre pathways in the living human brain. DTMRI can provide images that allow these pathways to be visualised in living human brains [1-3]. This opens up many new possibilities for testing how the pathways develop and age, and how they are disrupted in disease. Using funding from the Dr Hadwen Trust, Dr Johansen-Berg and Dr Behrens are using DTMRI to scan healthy people and those with disorders such as stroke, multiple sclerosis, schizophrenia and pain disorders [4]. The research will provide a general framework in which to test hypotheses about breakdowns in subcortical-cortical network connectivity in brain disorders, with a focus on chronic pain. DTMRI provides exciting and important new developments for the study of the healthy brain, as it enables the identification of specialised brain regions in living people [5-7]. For example, our grant-holders have recently identified, for the first time, sub-regions within the human premotor cortex, based on their patterns of connections with other areas. Previously, this region could only be reliably identified by microscopically examining slices of post-mortem brain.