myelin-oligodendrocyte-glycoprotein-(35-55) and Brain-Infarction

We aimed at validating a plasma biomarker for neuronal damage that can be used in acute and chronic models of neurological diseases.. We investigated two different models, middle cerebral artery occlusion followed by reperfusion and MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). In stroke experiments we measured infarct sizes by magnetic resonance imaging and vital stainings and correlated them with plasma levels of neuron specific enolase (NSE) at different time points after reperfusion. Equally, in EAE experiments, we correlated NSE levels with neurological scores and histopathological damage of axons at different time points. We detected plasma NSE levels by ELISA.. Plasma NSE levels correlated significantly with stroke size, EAE score and histopathological damage in EAE. Investigations into the dynamics of neuronal loss over time correlated well with the dynamics of NSE levels. NSE even predicted the onset of EAE, before clinical signs were recordable.. Plasma NSE is a valid and simple experimental biomarker that allows quantifying the degree of neuronal injury in a non-invasive approach.

Topics: Amyloid beta-Protein Precursor; Animals; Brain; Brain Infarction; Cells, Cultured; Disease Models, Animal; Embryo, Mammalian; Glutamic Acid; Infarction, Middle Cerebral Artery; L-Lactate Dehydrogenase; Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Neurons; Peptide Fragments; Phosphopyruvate Hydratase; Time Factors

Mucosal tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. In this work we demonstrate the reduction of infarct size following mucosal tolerance by myelin oligodendrocyte glycoprotein (MOG) (35-55) peptide in mouse stroke model. Nasal MOG was most efficacious and reduced ischemic infarct size by 70% at 24 h as well as improving behavior score. Using immunohistological methods and IL-10 -/- mice, we demonstrate the importance of IL-10-producing CD4+ T cells in the reduction of the ischemic infarct volume following middle cerebral artery occlusion (MCAO). Furthermore, adoptive transfer of CD4+ T cells from nasally tolerized mice to untreated mice prior to MCAO surgery significantly decreased stroke size (p<0.001 vs. control), whereas CD4+ T cells from nasally tolerized IL-10-deficient mice had no significant effect. Based on these results, modulation of cerebral inflammation by mucosal tolerance to myelin antigens may have applicability both as prophylactic therapy and treatment following ischemia attacks.

Topics: Analysis of Variance; Animals; Antigens, CD; Behavior, Animal; Brain Infarction; CD4-Positive T-Lymphocytes; Cells, Cultured; Cytokines; Disease Models, Animal; Drug Administration Routes; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Immune Tolerance; Immunohistochemistry; Infarction, Middle Cerebral Artery; Interleukin-10; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Immunological; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Severity of Illness Index; Stroke; Time Factors