title: CPI-1189 prevents apoptosis and reduces glial fibrillary acidic protein immunostaining in a TNF-alpha infusion model for AIDS dementia complex.
abstract: AIDS dementia complex (ADC) is characterized by increased apoptosis, gliosis, and oxidative stress in the CNS, as well as a compromised blood-brain barrier. TNF-alpha has been shown to be elevated in AIDS dementia complex brains and may contribute to AIDS dementia complex. To model elevated TNF-alpha in AIDS dementia complex, TNF-alpha was infused ICV bilaterally into rats for 3 days. TNF-alpha treatment increased apoptosis around the infusion site and selectively in the septum and corpus callosum. Co-administration of the synthetic antioxidant CPI-1189 prevented TNF-alpha induced apoptosis. Both TNF-alpha and CPI-1189 treatment suppressed glial fibrillary acidic protein (GFAP) staining at the infusion site. TNF-alpha did not significantly affect the integrity of the blood-brain barrier, but CPI-1189 treatment increased blood-brain barrier integrity at the infusion site. No effect of TNF-alpha or CPI-1189 treatment was found on measures of oxidative stress. These results support TNF-alpha as a key agent for increasing apoptosis in AIDS dementia complex. Additionally, CPI-1189 treatment may protect against TNF-alpha induced apoptosis and astrogliosis in AIDS dementia complex. Lastly, the toxic effect of TNF-alpha and the protective effect of CPI-1189 may not be mediated primarily through manipulation of classic reactive oxygen species.
authors.affiliation: Department of Psychology, University of South Florida, 4202 East Fowler Avenue, Tampa, FL 33620, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Bjugstad
authors.forename: W D
authors.initials: WD
authors.lastname: Flitter
authors.forename: W A
authors.initials: WA
authors.lastname: Garland
authors.forename: R M
authors.initials: RM
authors.lastname: Philpot
authors.forename: C L
authors.initials: CL
authors.lastname: Kirstein
authors.forename: G W
authors.initials: GW
authors.lastname: Arendash
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects*; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects; D002073:Butanes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003864:Depression, Chemical; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis*; D005911:Gliosis / Q000517:prevention & control*; D017665:Hydroxyl Radical / Q000378:metabolism; D007074:Immunoglobulin G / Q000032:analysis; D007276:Injections, Intraventricular; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000378:metabolism; D012688:Septum Pellucidum / Q000187:drug effects / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D002073:Butanes; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D012459:Salicylates; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; C406025:CPI 1189