Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury

Chen, Yong; Ruetzler, Christl; Pandipati, Sruthi; Spatz, Maria; McCarron, Richard M.; Becker, Kyra J.; Hallenbeck, John M.

doi:10.1073/pnas.2436538100

Cited by 80 publications

(81 citation statements)

References 48 publications

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“…This result conforms to our previous studies (Chen et al, 2003;Takeda et al, 2002) and confirms that immunological tolerance to E-selectin was induced by the intranasal administration of E-selectin.…”

Section: Delayed-type Hypersensitivityreactionsupporting

confidence: 93%

Mucosal Tolerization to E-Selectin Protects against Memory Dysfunction and White Matter Damage in a Vascular Cognitive Impairment Model

Wakita

Ruetzler

Illoh

et al. 2007

J Cereb Blood Flow Metab

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Vascular cognitive impairment (VCI) is the second most prevalent type of dementia in the world. The white matter damage that characterizes the common subcortical ischemic form of VCI can be modeled by ligating both common carotid arteries in the Wistar rat to induce protracted cerebral hypoperfusion. In this model, we find that repetitive intranasal administration of recombinant E-selectin to induce mucosal tolerance and to target immunomodulation to activating blood vessels potently suppresses both white matter (and possibly gray matter) damage and markers of vessel activation (tumor necrosis factor and E-selectin); it also preserves behavioral function in T-maze spontaneous alternation, T-maze spatial discrimination memory retention, and object recognition tests. Immunomodulation may be an effective novel strategy to prevent progression of VCI.

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Section: Delayed-type Hypersensitivityreactionsupporting

confidence: 93%

Mucosal Tolerization to E-Selectin Protects against Memory Dysfunction and White Matter Damage in a Vascular Cognitive Impairment Model

Wakita

Ruetzler

Illoh

et al. 2007

J Cereb Blood Flow Metab

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“…In mice, nasal tolerance to myelin oligodendrocyte glycoprotein (MOG; applied 3 times every other day) decreased by 70% the size of infarct (MCAO was induced 2 days after the last nasal administration) and reduced also the neurological deficit; this protective effect, which was associated with a marked increase in the anti-inflammatory cytokine IL-10 (but not of TGF-␤), was absent in IL-10 knockout mice (116, 117). Similar results were obtained with nasal tolerance to E-selectin, a cytokine-inducible adhesion molecule restricted to blood vessel endothelium activated by inflammatory stimuli (68).…”

Section: A Inflammatory Mechanismssupporting

confidence: 80%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

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Ischemic tolerance describes the adaptive biological response of cells and organs that is initiated by preconditioning (i.e., exposure to stressor of mild severity) and the associated period during which their resistance to ischemia is markedly increased. This topic is attracting much attention because preconditioning-induced ischemic tolerance is an effective experimental probe to understand how the brain protects itself. This review is focused on the molecular and related functional changes that are associated with, and may contribute to, brain ischemic tolerance. When the tolerant brain is subjected to ischemia, the resulting insult severity (i.e., residual blood flow, disruption of cellular transmembrane gradients) appears to be the same as in the naive brain, but the ensuing lesion is substantially reduced. This suggests that the adaptive changes in the tolerant brain may be primarily directed against postischemic and delayed processes that contribute to ischemic damage, but adaptive changes that are beneficial during the subsequent test insult cannot be ruled out. It has become clear that multiple effectors contribute to ischemic tolerance, including: 1) activation of fundamental cellular defense mechanisms such as antioxidant systems, heat shock proteins, and cell death/survival determinants; 2) responses at tissue level, especially reduced inflammatory responsiveness; and 3) a shift of the neuronal excitatory/inhibitory balance toward inhibition. Accordingly, an improved knowledge of preconditioning/ischemic tolerance should help us to identify neuroprotective strategies that are similar in nature to combination therapy, hence potentially capable of suppressing the multiple, parallel pathophysiological events that cause ischemic brain damage.

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“…In addition to this early nonspecific effect of T cells, is there room for any antigenmediated responses in acute stroke? Several lines of experimental evidence suggest that this might be the case [15][16][17][18][19][20][21], but further study is needed to confirm this possibility and dissect its potential contribution to the brain tissue fate and the potential relevance to human stroke. Indeed, our group described the presence of several brain antigens in the draining lymphoid tissue of patients with acute stroke that was correlated with the functional outcome of the patients at follow-up [22].…”

Section: Introductionmentioning

confidence: 99%