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Effects of a Cyclooxygenase-2 Preferential Inhibitor in Young Healthy Dogs Exposed to Air Pollution: A Pilot Study

期刊

TOXICOLOGIC PATHOLOGY
卷 37, 期 5, 页码 644-660

出版社

SAGE PUBLICATIONS INC
DOI: 10.1177/0192623309340277

关键词

Alzheimer's disease; air pollution; neuroinflammation; neuroprotection; Nimesulide (R); cerebrospinal fluid; dogs; brain MRI

资金

  1. National Science Foundation [0346458]
  2. Montana Board of Research and Commercialization Technology [04-06, 1KO1 NS 046410-01A1]
  3. NCRR [P20 RR015583]

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Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1 beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide (R)) versus 7 untreated litter-matched Mexico City dogs. Nimesulide (R) significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1 beta (p = .03), and heart IL1 beta (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of A beta(42) in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge.

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