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This content will become publicly available on January 27, 2019

Title: Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure

The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O 3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C 57BL/6 male mice, aged 8-10 weeks or 12–18 months were exposed to either filtered air (FA) or 1.0 ppm O 3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression was assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 hours post-O 3 exposure. Flow cytometry analysis of brains revealed increased microglia “activation” and presentation of CD11b, F4/80 and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O 3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O 3 insult. The aged cerebellum was particularly vulnerable to acute O 3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C + inflammatory monocytes aftermore » insult, which were not significantly increased in the young cerebellum. O 3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Furthermore, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O 3 exposure, leading to greater neuroinflammatory outcomes.« less
 [1] ;  [2] ;  [3] ;  [3] ;  [3] ;  [3] ;  [2] ;  [2] ;  [3]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States)
  2. Univ. of New Mexico Health Sciences Center, Albuquerque, NM (United States)
  3. Univ. of New Mexico, Albuquerque, NM (United States)
Publication Date:
Report Number(s):
Journal ID: ISSN 1096-6080
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Toxicological Sciences
Additional Journal Information:
Journal Volume: 163; Journal Issue: 1; Journal ID: ISSN 1096-6080
Oxford University Press
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
National Institutes of Health (NIH); USDOE
Country of Publication:
United States
60 APPLIED LIFE SCIENCES; Biological Science; neuroinflammation; microglia; aging; reproductive & developmental toxicology; ozone; blood–brain barrier; inhalation toxicology; respiratory toxicology
OSTI Identifier: