title: A novel phospholipid-based drug formulation, VP025, modulates age- and LPS-induced microglial activity in the rat.
abstract: BACKGROUND
  A common change that occurs with age in the central nervous system is an increase in microglial-associated inflammation. This is usually coupled with an increase in the concentration of the inflammatory cytokine interleukin-1beta (IL-1beta) in the hippocampus and an inhibition in long-term potentiation.
  
  
  OBJECTIVE
  To assess the effects of a novel preparation of phospholipid nanoparticles incorporating phosphatidylglycerol, VP025, on inflammatory changes in hippocampus of aged and lipopolysaccharide (LPS)-treated rats.
  
  
  RESULTS
  We report that a possible initial target cell of the putative anti-inflammatory actions of VP025 may be macrophages, as VP025 is engulfed by, and has the capacity to alter the activity of, these cells. VP025 reversed the increase in IFN-gamma concentration in supernatant taken from peritoneal macrophages harvested from LPS-treated rats. In addition, markers of microglial activity, major histocompatibility complex class II (MHC II) mRNA expression, CD40 expression and IL-1beta concentration were increased, and CD200 expression was reduced, in the hippocampus of these rats. VP025 reversed changes in CD40, IL-1beta and CD200 in aged rats, and also restored long-term potentiation in aged and LPS-treated rats.
  
  
  CONCLUSIONS
  We conclude that VP025 has the ability to modulate the activity of macrophage, microglia and neurons in response to stressors such as ageing and LPS treatment.
authors.affiliation: Vasogen Ireland Ltd., Trinity College Institute of Neuroscience, Physiology Department, Trinity College, Dublin, Ireland.
authors.forename: Darren S D
authors.initials: DS
authors.lastname: Martin
authors.forename: Michelle
authors.initials: M
authors.lastname: Walsh
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Miller
authors.forename: Helen E
authors.initials: HE
authors.lastname: Skerrett
authors.forename: Patricia
authors.initials: P
authors.lastname: Byrne
authors.forename: Arkady
authors.initials: A
authors.lastname: Mandel
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Bolton
authors.forename: Marina A
authors.initials: MA
authors.lastname: Lynch
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D004660:Encephalitis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005911:Gliosis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D053758:Nanoparticles / Q000737:chemistry; D019580:Perforant Pathway / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D010715:Phosphatidylglycerols; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma