Methods of suppressing microglial activation and systemic inflammatory responses

Abstract

Methods of suppressing the activation of microglial cells in the Central Nervous System (CNS), methods of ameliorating or treating the neurological effects of cerebral ischemia or cerebral inflammation, and methods of combating specific diseases that affect the CNS by administering a compound that binds to microglial receptors and prevents or reduces microglial activation are described. ApoE receptor binding peptides that may be used in the methods of the invention are also described, as are methods of using such peptides to treat peripheral inflammatory conditions such as sepsis. Also described are methods of screening compounds for the ability to suppress or reduce microglial activation.

1 - 80 . (canceled) 
     
     
         81 . A method of reducing neuronal cell injury associated with multiple sclerosis or experimental autoimmune encephalomyelitis (EAE) in a mammalian subject in need thereof comprising administering to the subject a composition comprising an ApoE peptide consisting essentially of SEQ ID NO: 10, in addition to one or more compounds selected from the group consisting of interferon (IFN) beta-1b, IFN beta-1a, glatiramer acetate, IV immunoglobulin, methotrexate, azathioprine, memantine, and NMDA receptor antagonists, and wherein said composition is administered in an amount that reduces neuronal cell injury associated with multiple sclerosis or EAE as compared to reduction that would occur in the absence of the composition. 
     
     
         82 . The method of  claim 81 , wherein the one or more compounds is administered concurrently with the ApoE composition. 
     
     
         83 . The method of  claim 81 , wherein the one or more compounds is administered sequentially with the ApoE composition. 
     
     
         84 . The method of  claim 81 , wherein the neuronal cell injury is associated with glutamate excitotoxicity. 
     
     
         85 . The method of  claim 84 , wherein the glutamate excitotoxicity is mediated by overstimulation of NMDA receptors. 
     
     
         86 . The method of  claim 81 , wherein the ApoE peptide is conjugated to a carrier molecule that increases transport of said peptide across the blood-brain barrier, compared to that which would occur in the absence of said carrier molecule. 
     
     
         87 . The method of  claim 86 , wherein the carrier molecule is selected from the group consisting of pyridinium, fatty acids, inositol, cholesterol, glucose derivatives, hemoglobin, lysozyme, cytochrome c, ceruloplasmin, calmodulin, ubiquitin, substance P, histone, insulin and transferrin and peptides thereof, lipid vesicles, and liposomes.