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Inflammation in stroke

AuthorsPlanas, Anna M. ; Chamorro, Ángel
Adhesion molecules
Middle cerebral artery occlusion
Issue DateFeb-2006
PublisherRPA Publishers
CitationInternational Journal of Neuroprotection and Neurogeneration 2(2): 110-119 (2006)
AbstractObjectives: Acute ischemia in the brain triggers multiple cellular and tissular reactions that can cause neuronal cell death. Injury may expand with time by propagation of damage to neighbouring and even to remote areas, or can progress to delayed neuronal death. The actual contribution of inflammation to primary and secondary ischemic injury is not well established. Clinical evidence supports that inflammation during the acute phase of stroke is related to bad outcome. Animal studies have also shown increase of inflammatory markers after experimental ischemia. However, the effects of some pro-inflammatory cytokines are controversial as benefits against ischemic damage were shown in pre-clinical studies. Methodology: Inflammatory markers, such as the erythrocyte sedimentation rate (ESR), levels of cytokines and adhesion molecules, were measured in plasma and CSF of stroke patients at different time points after stroke onset and were correlated to the clinical outcome. The expression of adhesion molecules (ICAM-1 and VCAM-1) was measured in rats subjected to transient middle cerebral artery (MCA) occlusion. Leukocyte infiltration was prevented in rats by systemic administration of blocking antibodies against adhesion molecules or by inducing neutropenia, and infarct volume was determined 1 or 2 days latter. The effect of preventing leukocyte infiltration on matrix metalloproteinase-9 (MMP-9) expression in brain was evaluated. Results: High plasma levels of pro-inflammatory cytokines (such as IL-6 and TNF-α) during the first hours after the onset of stroke were predictors of poor outcome, and increased to higher levels in patients who deteriorate. In addition, the ESR was an independent predictor of poor clinical outcome. Also, low plasma levels of the anti-inflammatory cytokine IL-10 correlate with poor clinical outcome. Unfractioned heparin prevented more effectively than aspirin the increase of some adhesion molecules including VCAM-1 in plasma, and the effect independently decreased functional damage in patients. In ischemic rats we showed increased expression of VCAM-1 and ICAM-1 in the microvasculature. VCAM-1 expression was attenuated by a protective treatment with heparin, which also increased plasma levels of IL-10. Blocking ICAM-1 or neutropenia prevented neutrophil infiltration and MMP-9 increase after ischemia. However, we found no evidence of infarct volume reduction at 24h in neutropenic animals but some trend to reduced damage was found at 3 days, suggesting protection against delayed damage. Conclusion: In patients, high plasma levels of inflammatory markers at hospital entry (ESR, IL-6, TNF-α, ICAM-1 and VCAM-1) result in part from the extent of ongoing tissue damage but they also anticipate further growing of tissue damage and clinical deterioration, as do low levels of an anti-inflammatory cytokine (IL-10). In animals, preventing neutrophil infiltration seemed not to be beneficial during the first 24h after ischemia, but suggested some positive effects at delayed measurement. The actual contribution of inflammation to ischemic damage is complex and still controversial. Discrepancies between preclinical and clinical observations deserve further elucidation. © RPA Publications. All rights reserved.
Identifiersissn: 1745-1183
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