Chronic exposure to low doses of ozone produces a state of oxidative stress and blood-brain barrier damage in the hippocampus of rat

Selva Rivas-Arancibia, Luis Fernando Hernández-Zimbrón, Erika Rodríguez-Martínez, Gabino Borgonio-Pérez, Varsha Velumani, Josefina Durán-Bedolla

Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, México.
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México D. F., México.

DOI: 10.4236/abb.2013.411A2004                

Abstract

Chronic exposure to low doses of ozone similar to a day of high pollution in Mexico City causes a state of oxidative stress. This produces a progressive neurodegeneration in hippocampus of rats exposed to the gas. The aim of this study was to analyze the effect of chronic exposure on the changes in the blood-brain barrier in rats exposed to low doses of ozone. Method: each group received one of the following treatments, control group received air without ozone, and groups 2, 3, 4, 5, and 6 received ozone doses of 0.25 ppm for 4 h daily during 7, 15, 30, 60 and 90 days respectively. Each group was processed to inmunohistochemical technique against of the following antibody: blood-brain barrier, guanylyl cyclase, Iba-1, GFAP, NFκ-B, TNF-α. The results show that there is a correlation between the time exposure of ozone and the progressive damage, on the blood-brain barrier rupture, finally causing edema of endothelial cell, increase in guanylyl cyclase type 1, thickening of the processes and astrocytes foot, and an increase in the expression of factors NFκ-B and TNF-α at 30 and 60 days of exposure to this gas. All the above indicates that the chronic state of oxidative stress causes a neurodegeneration process, accompanied by disruption of the blood-brain barrier likely to occur in the Alzheimer’s disease. 

Keywords

Ozone; Oxidative Stress; Blood-Brain Barrier; Neurodegenerative Diseases

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Sierra-Vargas, M.P. and Teran, L.M. (2012) Air pollution: Impact and prevention. Respirology, 17, 1031-1038. http://dx.doi.org/10.1111/j.1440-1843.2012.02213.x
[2]	Billionnet, C., Sherrill, D., Annesi-Maesano, I., GERIE, S. (2012) Estimating the health effects of exposure to multi-pollutant mixture. Annals of Epidemiology, 22, 126-141. http://dx.doi.org/10.1016/j.annepidem.2011.11.004
[3]	Grella, E., Paciocco, G., Caterino, U. and Mazzarella, G. (2002) Respiratory function and atmospheric pollution. Monaldi Archives for Chest Disease, 57, 196-199.
[4]	Delzell Jr., J.E. (2013) Common lung conditions: Environmental pollutants and lung disease. FP Essentials, 409, 32-42.
[5]	Pope, C.A., Verrier, R.L., Lovett, E.G., Larson, A.C., Raizenne, M.E., Kanner, R.E., Schwartz, J., Villegas, G.M., Gold, D.R. and Dockery, D.W. (1999) Heart rate variability associated with particulate air pollution. American Heart Journal, 138, 890-899. http://dx.doi.org/10.1016/S0002-8703(99)70014-1
[6]	Rivas-Arancibia, S., Guevara-Guzmán, R., López-Vidal, Y., Rodríguez-Martínez, E., Zanardo-Gomes, M., Angoa-Pérez, M. and Raisman-Vozari, R. (2010) Oxidative stress caused by ozone exposure induces loss of brain repair in the hippocampus of adult rats. Toxicological Science, 113,187-197.
[7]	Rodríguez-Martínez, E., Martínez, F., Espinosa-García, M.T., Maldonado, P. and Rivas-Arancibia, S. (2013) Mitochondrial dysfunction in the hippocampus of rats caused by chronic oxidative stress. Neuroscience, 252, 384-395. http://dx.doi.org/10.1016/j.neuroscience.2013.08.018
[8]	Iles, K.E. and Jay, F. (2002) Macrophage signaling and respiratory burst. Immunological Research, 26, 95-105. http://dx.doi.org/10.1385/IR:26:1-3:095
[9]	Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T., Mazur, M. and Telser, J. (2007) Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry and Cell Biology, 39, 44-84.
[10]	Banks, W.A. and Erickson, M.A. (2010) The blood-brain barrier and immune function and dysfunction. Neurobiology of Disease, 37, 26-32. http://dx.doi.org/10.1016/j.nbd.2009.07.031
[11]	Stolp, H.B., Liddelow, S.A., Sá-Pereira, I., Dziegielewska, K.M. and Saunders, N.R. (2013) Immune responses at brain barriers and implications for brain development and neurological function in later life. Frontiers in Integrative Neuroscience, 7, 61. http://dx.doi.org/10.3389/fnint.2013.00061
[12]	Enciu, A.M., Gherghiceanu, M. and Popescu, B.O. (2013) Triggers and effectors of oxidative stress at blood-brain barrier level: Relevance for brain ageing and neurodegeneration. Oxidative Medicine and Cellular Longevity, 2013, 297512. http://dx.doi.org/10.1155/2013/297512
[13]	Dorheim, M.A., Tracey. W.R., Pollock, J.S. and Grammas, P. (1994) Nitric oxide synthase activity is elevated in brain microvessels in Alzheimer’s disease. Biochemical and Biophysical Research Communications, 30, 659-665. http://dx.doi.org/10.1006/bbrc.1994.2716
[14]	Erickson, M.A. and Banks, W.A. (2013) Blood-brain barrier dysfunction as a cause and consequence of Alzheimer’s disease. Journal of Cerebral Blood Flow & Metabolism, 33, 1500-1513. http://dx.doi.org/10.1038/jcbfm.2013.135