ABSTRACT
OBJECTIVE: To study the effect of mucosal toleration to E-selectin on cerebral ischemia-reperfusion injury in rats and associated mechanisms. METHODS: Rats were exposed to intranasal administration of E-selectin or PBS every other day for 10 days (single-tolerization group) or on two tolerization schedules separated by 11 days (booster-tolerization group). Control group received middle cerebral artery occlusion (MCAO) only. MCAO was performed 48 h after the last dose of E-selectin or PBS. After 2 h ischemia and 22 h reperfusion, the rats were killed. We examined the regional cerebral blood flow, neurological testing, frequencies of CD4+ T and CD8+ T lymphocytes in blood, plasma SOD activity, infarct volumes, and mRNA expressions of IL-10, TGF-beta(1), E-selectin, ICAM-1 and LFA-1 in the ischemic brain tissues. RESULTS: There were 30.25% (P<0.05) decreases of infarction volumes in the E-selectin booster group accompanied by decreased neurological deficit scores compared with PBS group. Compared with PBS-treated rats, CD8-positive cells were significantly decreased (27.4%, P<0.05), CD4-positive cells tended to increase (P>0.05), SOD activity was obviously increased (P<0.05), mRNA levels of IL-10 were markedly increased (21.0%, P<0.05) and TGF-beta(1) showed an upward trend (6.2%, P>0.05), mRNA levels of E-selectin were prominently decreased (28.7%, P<0.01) and ICAM-1 and LFA-1 had downward trends (P>0.05) in E-selectin booster animals. CONCLUSIONS: Mucosal tolerance to E-selectin after booster tolerization could relieve cerebral ischemia-reperfusion injury and induce ischemia tolerance in Wistar rats. The mechanisms may involve decreased frequencies of CD8+ T cells in blood, increased plasma SOD activity, heightened mRNA expression of IL-10 and lowered mRNA expression of E-selectin in the ischemic hemisphere.
Subject(s)
E-Selectin/administration & dosage , Immune Tolerance/drug effects , Neuroprotective Agents/administration & dosage , Reperfusion Injury/prevention & control , Reperfusion Injury/physiopathology , Administration, Intranasal , Animals , CD4-Positive T-Lymphocytes/physiology , CD8-Positive T-Lymphocytes/physiology , Cerebrovascular Circulation/drug effects , Cerebrovascular Circulation/physiology , Disease Models, Animal , E-Selectin/genetics , E-Selectin/metabolism , Flow Cytometry , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunology , Immune Tolerance/physiology , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , Lymphocyte Function-Associated Antigen-1/genetics , Lymphocyte Function-Associated Antigen-1/metabolism , Male , Neurologic Examination , RNA, Messenger/metabolism , Rats , Rats, Wistar , Reperfusion Injury/pathology , Superoxide Dismutase/blood , Time Factors , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolismABSTRACT
E-selectin is an inducible adhesion molecule,and it is correlated with various molecules during cerebral ischemia/reperfusion injury.This article mainly reviews the relationship between E-selectin and intracellular adhesion molecule-1,tumor necrosis factor-?,NF-kB,leucocyte function-associated antigen-1 in cerebral ischemia/reperfusion injury,so as to provide assistance for E-selectin in the prevention,diagnosis and treatment of ischemic cerebrovascular disease.
