Long term immunologic consequences of experimental stroke and mucosal tolerance
J. Michael Gee,Dannielle Zierath,Jessica Hadwin,Anna V. Savos,Angela Kalil,Matthew Thullbery,Kyra J. Becker +6 more
TLDR
Induction of immunological tolerance to MBP is associated with improved outcome after stroke, however, this study raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.Abstract:
An inflammatory insult following middle cerebral artery occlusion (MCAO) is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP). Induction of immunologic tolerance to brain antigens prior to MCAO prevents this deleterious autoimmune response and is associated with better functional outcome early after stroke. In this study, we sought to determine the long term immunologic consequences of experimental stroke and induction of mucosal tolerance. Male Lewis rats were tolerized to MBP or ovalbumin (OVA) by intranasal administration prior to MCAO and administration of lipopolysaccharide (LPS). Neurological outcome was assessed at set points after MCAO and animals sacrificed at 3 months; the immune response to MBP in brain and spleen was determined using ELISPOT assay and degree of cellular inflammatory brain infiltrate assessed by immunocytochemistry. Animals that developed a pro-inflammatory (TH 1) response to MBP experienced worse outcome, while those that developed a regulatory response (TREG) experienced better outcome. A TREG response in spleen was also associated with decreased inflammation and an increase in the number of FoxP3 positive cells in brain. In this study, tolerization to MBP prior to MCAO was associated with a tendency to develop a TH 1 response to MBP by 3 months after MCAO. These data show that induction of immunological tolerance to MBP is associated with improved outcome after stroke. This study, however, raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.read more
Citations
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Book ChapterDOI
A Review of Neuroinflammatory Mechanisms in Ischemic Stroke: Background and Therapeutic Approaches
TL;DR: The main processes in the background of arterial vessel occlusion, ensuing tissue damage and following reparation of ischemic stroke are introduced and possible opportunities that can be considered in development or clinical applications of neuroprotectants are raised.
DissertationDOI
Lokalisierung und Charakterisierung Foxp3+ regulatorischer T-Zellen bis zu 30 Tage nach mechanischer und ischämischer Läsion des Gehirns
TL;DR: This study sought to analyse the temporal distribution, location, induction and effect of Tregs on days 7, 14 and 30 following entorhinale cortex lesion (ECL) and cerebral infarction in mice after transient middle cerebral artery occlusion (MCAO).
Book ChapterDOI
Neuroimmune and Systemic Manifestations of Neuroinflammation in the Temporomandibular Joint and Related Disorders
TL;DR: Temporomandibular disorders are a group of pathologies affecting the TMJ, the muscles of mastication, and the related ligaments causing the joint dysfunction, and is considered to be among the most complex and yet common conditions involving orofacial pain.
Book ChapterDOI
Tolerization to Brain and Vascular Antigens: Targeting Autoimmunity After Acute Brain Injuries and Preventing Stroke
TL;DR: This chapter addresses the use of mucosal tolerance to both prevent and treat ischemic stroke.
Book ChapterDOI
Immunological Mechanisms of Inflammation
TL;DR: A large number of these deaths were due to coronary heart disease and 6.2 million to stroke, and the number of people dying from these diseases is likely to be underestimated.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
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Halina Offner,Sandhya Subramanian,Susan M. Parker,Michael Afentoulis,Arthur A. Vandenbark,Arthur A. Vandenbark,Patricia D. Hurn +6 more
TL;DR: Data show for the first time that focal cerebral ischemia results in dynamic and widespread activation of inflammatory cytokines, chemokines, and CCR in the peripheral immune system.