title: Inflammatory cells and cytokines in the olfactory bulb of a rat model of neuroinflammation; insights into neurodegeneration?
abstract: This study examined inflammatory cell and cytokine production in brain tissue from a lipopolysaccharide (LPS)-treated rat model that mimics many of the neuropathologic changes associated with neurodegenerative diseases We also monitored the appearance of a glial cell line-derived neurotrophic factor (GDNF) and circulating nitric oxide (NO) levels, as well as an immune system-associated cells in a selected area of the brain, the olfactory lobe. The studies were based on the hypothesis that LPS treatment stimulates temporal changes within the brain and that these responses include immune cell recruitment, increased tissue levels of immune modulating cytokines and NO, as well as greater glial cell activation resulting in increased production of GDNF. As previously reported by other investigators, our animal model of systemic LPS treatment leads to an increase in the concentrations of circulating cytokines, including TNF-α, IL-Iβ, and IL-6, with a maximum response 6 h post LPS administration. Concomitant with cytokine elevations, circulating NO levels were elevated for several hours post LPS administration. The brain content of the GDNF was also elevated over a similar time frame. Lymphocytes, neutrophils, macrophages, plasma cells, and cytokines were all seen in various areas of LPS-treated brains, often around blood vessels associated with the meninges, with these localizations possibly indicating involvement of both the blood-brain and blood-cerebral spinal fluid barriers in these inflammatory episodes. Our results suggest an involvement of both the peripheral and the central nervous system immune components in response to inflammation and inflammatory episodes. This leads us to propose that inflammation initiates an immune response by activating both microglia and astrocytes and that the presence of continuing and increasing proinflammatory mechanisms results in a situation, where cellular protective mechanisms are overcome and the more susceptible cells enter into cell death pathways, initiating a train of events that is a major part of neurodegeneration.
authors.affiliation: Department of Anesthesiology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors.forename: Marie-Francoise
authors.initials: MF
authors.lastname: Doursout
authors.forename: Michael S
authors.initials: MS
authors.lastname: Schurdell
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Young
authors.forename: Uzondu
authors.initials: U
authors.lastname: Osuagwu
authors.forename: Diana M
authors.initials: DM
authors.lastname: Hook
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Poindexter
authors.forename: Mya C
authors.initials: MC
authors.lastname: Schiess
authors.forename: Diane L M
authors.initials: DL
authors.lastname: Bick
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Bick
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D019636:Neurodegenerative Diseases / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D009830:Olfactory Bulb / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide