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      Relation between Laterality and Immune Response after Acute Cerebral Ischemia

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          Abstract

          Objective: During the last 2 decades, right/left hemisphere dominance was supposed to affect the immune system differently. Experimental and clinical observations indicate that the left hemisphere plays a crucial role in the development of the immune system. The true relationship between immune response and acute ischemic stroke laterality remains to be elucidated. Methods: We studied acute right-handed stroke patients admitted to a single acute neurology department with a specialized stroke unit. Being part of our clinical protocol, blood samples were taken within the first 24 h after the onset of stroke symptoms. The medical record of each patient was reviewed, and demographic, clinical laboratory (key criteria: C-reactive protein, CRP, and white blood cell count, WBC) and neuroimaging information was retrieved. All data were presented descriptively, and bivariate test statistics, ANOVA (log-transformed data) or linear correlations were calculated. Results: Fifty-six of the 187 patients admitted to our Stroke Unit between October 2003 and March 2004 with different stroke subtypes according to the TOAST criteria were retrospectively evaluated in order to characterize the impact of stroke laterality on immunoregulatory response measured by CRP levels and WBC. Correlation analysis revealed that left-sided ischemic stroke yielded a significantly higher correlation between CRP levels and WBC. Following left-sided stroke, a more marked variability in CRP and WBC was found compared to patients with right-sided ischemic stroke, although ANOVA did not show significant differences between immune response values as a function of stroke subtypes. Conclusions: We identified an association between stroke laterality and immunoregulatory response in patients with acute ischemic stroke. Left-sided stroke may be considered as a direct risk factor for infectious disease or immune deficits and should attract special attention. However, these preliminary results need be confirmed by controlled studies.

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          Most cited references 6

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          Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats.

          The left and right neocortex of the brain has been shown to exert asymmetrical effects on the immune system. In the present study, we used a middle cerebral artery (MCA) occlusion model in Wistar rats to analyze the influence of unilateral CNS ischemia on spleen cell number and function. The occlusion time was 1 h, followed by reperfusion with survival for 0, 2, 7, 14, and 28 days. Changes in plasma norepinephrine levels were used as an index of peripheral sympathetic activity. Results showed that the total number of spleen cells significantly decreased after 2-28 days of survival in animals with cerebral ischemia compared to sham-operated controls. There was no change in the percentage of CD5(+)-CD4(+) T cells, MHC class II(+) cells, or ED1(+) macrophages. However, the percentage of CD5(+)-CD8(+) T cells decreased at 2 days, resulting in an increased CD4/CD8 ratio, and both parameters returned to control levels after 7 days. Mitogen-induced T and B lymphocyte proliferation increased after 0-28 days post-ischemia independently of the mitogen used. There was no difference in immune response or norepinephrine levels between left and right MCA occlusions. These results are consistent with the notion that cerebral ischemia induces mobilization of certain immune cells from the periphery to the brain, where they may contribute to the local inflammatory response. Additionally, the data indicate that cerebral ischemia is followed by a systemic activation of T and B lymphocytes. Absence of asymmetric effects of left versus right stroke, and failure to demonstrate any suppressive effects of left-sided lesions on lymphocyte proliferation, probably reflects the fact that these large cerebral ischemic lesions affect both cortical and subcortical areas.
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            Localization of the brain lesion affects the lateralization of T-lymphocyte dependent cutaneous inflammation. Evidence for an immunoregulatory role of the right frontal cortex-putamen region.

            We have previously demonstrated that brain lesions caused by stroke led to the lateralization of T-cell dependent inflammation. The purpose of this study was to assess the impact of localization of the brain lesion on lateralization of immune responsiveness. The delayed-type hypersensitivity (DTH) reaction was used as an in vivo measure of antigen specific T-lymphocyte reactivity. All stroke patients were examined with computed scan tomography (CT) of the brain to ascertain the localization and extent of the brain lesion. Patients with right-sided brain lesions displayed significantly larger (P = 0.008) DTH responses on the paretic side compared to the contralateral side. Detailed analysis of the localization of the brain lesion revealed that infarcts encompassing frontal lobe-putamen led to significantly larger (P = 0.007) DTH responses on the paretic side compared to the contralateral side. Localization of the brain lesion affects the lateralization of DTH, supporting an asymmetrical modulation of the immune response. In addition, our study points to the frontal cortex-putamen as a putative brain centre regulating the magnitude of immune responses.
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              Lateralized neocortical control of T lymphocyte export from the thymus I. Increased export after left cortical stimulation in behaviorally active rats, mediated by sympathetic pathways in the upper spinal cord.

              Electrical stimulation of left temporo-parieto-occipital (TPO) cortex in adult male Wistar rats during their behaviorally active phase (nighttime) transiently increased circulating levels of CD4+ and CD8+ T lymphocytes. Comparable stimulation of this cortex on the right decreased circulating levels of these cells. Responses to left or right cortical stimulation were diminished or absent in behaviorally inactive rats (daytime). Since blood glucocorticoid levels were similar before and after left or right stimulation, they did not appear to account for the lateralized changes observed. These lateralized effects were mediated by spinal cord autonomic pathways emerging at Tl-T7 levels. In adult thymectomized rats, CD4+ and CD8+ T cells failed to increase after left sided stimulation. The results suggest that lateralized cerebral cortical functions can acutely and differentially influence blood T cell subset numbers. The results demonstrate a direct neocortical influence on thymic export of mature T cells, mediated by the sympathetic nervous system.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2006
                August 2006
                08 August 2006
                : 13
                : 1
                : 8-12
                Affiliations
                Department of Neurology, University of Regensburg, Regensburg, Germany
                Article
                92108 Neuroimmunomodulation 2006;13:8–12
                10.1159/000092108
                16612132
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 1, References: 13, Pages: 5
                Categories
                Original Paper

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