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      Relation between laterality and immune response after acute cerebral ischemia.

      Neuroimmunomodulation
      Acute Disease, Adult, Aged, Brain Ischemia, blood, immunology, physiopathology, C-Reactive Protein, metabolism, Cerebral Cortex, blood supply, Cohort Studies, Female, Functional Laterality, physiology, Humans, Immune System, Immune Tolerance, Immunocompromised Host, Leukocyte Count, Male, Middle Aged, Neuroimmunomodulation, Predictive Value of Tests, Retrospective Studies, Risk Factors, Stroke

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          Abstract

          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. 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. 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. 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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          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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            Levene tests of homogeneity of variance for general block and treatment designs.

            This article develops a weighted least squares version of Levene's test of homogeneity of variance for a general design, available both for univariate and multivariate situations. When the design is balanced, the univariate and two common multivariate test statistics turn out to be proportional to the corresponding ordinary least squares test statistics obtained from an analysis of variance of the absolute values of the standardized mean-based residuals from the original analysis of the data. The constant of proportionality is simply a design-dependent multiplier (which does not necessarily tend to unity). Explicit results are presented for randomized block and Latin square designs and are illustrated for factorial treatment designs and split-plot experiments. The distribution of the univariate test statistic is close to a standard F-distribution, although it can be slightly underdispersed. For a complex design, the test assesses homogeneity of variance across blocks, treatments, or treatment factors and offers an objective interpretation of residual plots.
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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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