| Sign In to gain access to subscriptions and/or personal tools. |
Effects of a Cyclooxygenase-2 Preferential Inhibitor in Young Healthy Dogs Exposed to Air Pollution: A Pilot Study
1 Instituto Nacional de Pediatría, Mexico City, Mexico Correspondence: Address correspondence to: Lilian Calderón-Garcidueñas, MD, PhD, Center for Structural and Functional Neurosciences, College of Health Professions and Biomedical Sciences, University of Montana, 32 Campus Drive, 289 Skaggs Bldg, Missoula MT 59812, USA; phone: 406-243-4785; fax: 406-243-2807; e-mail:lilian.calderon-garciduenas{at}umontana.edu. Address reprint requests to: Robert R. Maronpot, DVM, MS, MPH, Experimental Pathology Laboratories, Inc, PO Box 12766, Research Triangle Park, NC 27709, USA; phone: 919-851-2236; e-mail:maronpot{at}earthlink.net. 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 1β, 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®) versus 7 untreated litter-matched Mexico City dogs. Nimesulide® significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1β (p = .03), and heart IL1β (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 Aβ42 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.
Key Words: Alzheimer’s disease • air pollution • neuroinflammation • neuroprotection • Nimesulide® • cerebrospinal fluid • dogs • brain MRI Abbreviations: AD, Alzheimer’s disease • ADDL, amyloid-derived diffusible ligand • Aβ42, beta amyloid 42 • BBB, blood-brain-barrier • COX2, cyclooxygenase-2 • GFAP, glial fibrillary acidic protein • IL1β, interleukin1β • IHC, immunohistochemistry • INP, Instituto Nacional de Pediatría • MC, Mexico City • OB, olfactory bulb • O3, ozone • PM, particulate matter • PGE2, prostaglandin E2 • MRI, magnetic resonance imaging • NSAIDs, nonsteroidal anti-inflammatory drugs • UFPM, ultrafine particulate matter
Toxicologic Pathology, Vol. 37, No. 5,
644-660 (2009) |
||||
 |
|
|
 |
|
Sign In to gain access to subscriptions and/or personal tools.
