London, United Kingdom 2013 7 Experimental studies A 15:30 - 15:40 REGULATORY T CELLS MODULATE INFLAMMATION AND REDUCE INFARCT VOLUME IN EXPERIMENTAL ISCHEMIA. D. Brea1, J. Agulla2, D. Barral3, F. Campos4, J. Castillo5, A. Dávalos6, P. Ramos-Cabrer7 Department of Neurosciences, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias I Pujol., Badalona, SPAIN1,Department of Neurology, Clinical Neurosci-ences Research Laboratory, Hospital Clínico Universitario., Santiago de Compostela, SPAIN2, Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Uni-versitario., Santiago de Compostela, SPAIN3, Department of Neurology, Clinical Neurosci-ences Research Laboratory, Hospital Clínico Universitario., Santiago de Compostela, SPAIN4, Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Uni-versitario., Santiago de Compostela, SPAIN5, Department of Neurosciences, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias I Pujol., Badalona, SPAIN6, Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario., Santiago de Compostela, SPAIN7 Background: Regulatory T cells (Treg cells) are a subpopulation of CD4+ T cells with immuno-suppressor/ anti-inflammatory properties. Because brain ischemia triggers an intense inflamma-tory response, the objective of this study was to demonstrate the role of Treg cells as neuropro-tective agents. Methods: Twenty Sprague-Dawley rats were subjected to transient occlusion of the cerebral middle artery (tMCAO). After a 75min occlusion, the rats were randomized and in-travenously treated with 3x106 Treg cells (Treg-treated) or PBS (control). Brain infarct volume and edema were evaluated at days 1, 3, 7 and 10 by T2W-MRI (Magnetic Resonance Imaging). At day 10, the rats’ brains were extracted for analysis by ELISA (for IL-1β and TNF-α), west-ern blot (for FoxP3) and immunohistochemistry (for macrophages and activated microglia). Results: Treg-treated animals showed smaller infarcts than control rats at day 3 (198.01±29.61 vs 349.84±48.50 mm3; p=0.027), day 7 (149.16±19.43 vs 227.24±30.64 mm3; p=0.049) and day 10 (120.38±12.94 vs 186.71±26.88 mm3; p=0.041). Treg-treated animals showed a high-er expression of FoxP3 (3.5±0.3 vs 2.3±0.3 AU; p=0.015), lower levels of IL-1β (19.46±1.02 vs 25.92±2.58 pg/mg; p=0.048) and lower numbers of macrophages (17.93±1.07 vs 28.8±0.7 cells; p=0.005) and activated microglia (18.23±1.04 vs 24.85±0.55 cells; p=0.018) than control animals in the infarcted hemisphere. Conclusions: Treatment with Treg cells 2 h after experi-mental ischemia reduces infarct volume and inflammation in the ischemic tissue. A reduction in infarct volume is accompanied by a reduction in inflammatory markers and by an increase in the expression of FoxP3 (a Treg marker) in the infarcted brain hemisphere. Cerebrovasc Dis 2013; 35 (suppl 3)1-854 59 6 Experimental studies A 15:20 - 15:30 Anatomically-appropriate chronic behavioral deficits in a model of thalamocapsular lacu-nar- type infarction M.B. Jensen1, L.D. Jager2, L.K. Cohen3 University of Wisconsin, Madison, USA1,University of Wisconsin, Madison, USA2, Universi-ty of Wisconsin, Madison, USA3 Background: The neuroanatomical correlates of recovery after cerebral infarction can be diffi-cult to assess with injury centered on the complex neuronal networks of the cerebral cortex or striatum. This may be better evaluated by smaller, targeted infarction of subcortical pathways with well-defined structure and function. Methods: We disrupted the subcortical somatosensory and corticofugal tracts at the ventral posterior nuclei of the thalamus and the adjacent internal capsule in five adult male rats by in-jection of 0.125 ug of endothelin-1 to induce lacunar-type infarction, followed by extensive be-havioral evaluation for gross motor, fine motor, and somatosensory function at baseline and five weeks after infarction. Results: Gross motor function showed chronic deficits of 37% on the rotarod (p>0.05), 30% on the corner test (p>0.05), and 10% on the elevated body swing test (p>0.05). Fine motor func-tion showed chronic deficits of 66% on the staircase test (p=0.02). Somatosensory function showed chronic deficits of 66% on vibrissae placing (p=0.03), and 7% on the tape bracelet test (p>0.05). The mean volume of infarction of the lateral thalamus and adjacent internal capsule was 12% relative to the unlesioned hemisphere. Conclusions: This ischemic stroke model system could be useful for studying the neuroanato-my of ischemic stroke recovery based on the specificity of deficits referable to the injured neu-ral pathways. The evaluation of recovery treatments dependent on anatomical considerations, such as neural cell grafting for repair of specific central nervous system tracts, could, in partic-ular, be more fully evaluated for tract connectivity.
Karger_ESC London_2013
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