we hypothesized that ozone-adaptation is linked to diminution of neuroendocrine stress-axes activation and glucocorticoid levels. Male Wistar-Kyoto-rats (12-week-old) were injected with vehicle or a therapeutically-relevant dexamethasone dose (0.01-mg/kg/day; intraperitoneal) for 1-month to determine if suppression of glucocorticoid signaling was linked to adaptation. Vehicle- and dexamethasone-treated rats were exposed to air or 0.8-ppm ozone, 4 hours/dayx2 or 4 days to assess the impacts of acute exposure and adaptation, respectively. This dataset is associated with the following publication: Heinriquez, A., S. Snow, J. Dye, M.C. Schladweiler, D. Alewel, C. Miller, and U. Kodavanti. The contribution of the neuroendocrine system to adaption after repeated daily ozone exposure in rats. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, USA, 447(116085): 1, (2022).

Dorsal third ventricle infusions of the alpha 2 adrenergic receptor antagonist, mianserin- which increases brain concentrations of dopamine, serotonin, and acetylcholine, or the glucocorticoid receptor antagonist, mifepristone, were performed in male WKY rats prior to acute ozone exposure at 0.8 ppm for 4 hours. This experiment was designed to target hippocampal and hypothalamic neuromodulation to determine the role of indoleamines, monoamines, and glucocorticoids in mediating the systemic and pulmonary effects to ozone exposure.

This data set was used for the manuscript titled "Ozone-induced Changes in Oxidative Stress Parameters in Brain regions of Adult, Middle-age, and Senescent Brown Norway Rats". It includes various biochemical endpoints and neurobehavior. This dataset is associated with the following publication: Kodavanti, P.R., M. Valdez, J. Richards, D. Agina-Obu, P. Phillips, K. Jarema, and U. Kodavanti. Ozone-induced changes in oxidative stress parameters in brain regions of adult, middle-age, and senescent Brown Norway rats. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, USA, 410: 115351, (2020).

Ozone exposure induces neuroendocrine stress response, which causes lymphopenia. We hypothesized that ozone-induced increases in stress hormones will temporally follow changes in circulating granulocytes, monocytes and lymphocyte subpopulations. The goal of this study was to chronicle the changes in circulating stress hormones, cytokines, and leukocyte trafficking during 4-hour exposure to ozone. Male Wistar Kyoto rats were exposed to air or ozone (0.4 or 0.8 ppm) for 0.5, 1, 2, or 4 hours. After each time point, we assessed, circulating stress hormones and cytokines, lung gene expression, and live and apoptotic granulocytes, monocytes (classical and non-classical), and lymphocytes (B, Th and Tc) in blood, thymus and spleen using flow cytometry. This dataset is associated with the following publication: Henriquez, A., W. Williams, S. Snow, M.C. Schladweiler, C. Fisher, M. Hargrove, D. Alewel, C. Colonna, S. Gavett, C. Miller, and U. Kodavanti. The Dynamicity of Acute Ozone-Induced Systemic Leukocyte Trafficking and Adrenal-Derived Stress Hormones. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 458(152823): 1, (2021).

Ozone exposure induces neuroendocrine stress response, which causes lymphopenia. We hypothesized that ozone-induced increases in stress hormones will temporally follow changes in circulating granulocytes, monocytes and lymphocyte subpopulations. The goal of this study was to chronicle the changes in circulating stress hormones, cytokines, and leukocyte trafficking during 4-hour exposure to ozone. Male Wistar Kyoto rats were exposed to air or ozone (0.4 or 0.8 ppm) for 0.5, 1, 2, or 4 hours. After each time point, we assessed, circulating stress hormones and cytokines, lung gene expression, and live and apoptotic granulocytes, monocytes (classical and non-classical), and lymphocytes (B, Th and Tc) in blood, thymus and spleen using flow cytometry. This dataset is associated with the following publication: Henriquez, A., W. Williams, S. Snow, M.C. Schladweiler, C. Fisher, M. Hargrove, D. Alewel, C. Colonna, S. Gavett, C. Miller, and U. Kodavanti. The Dynamicity of Acute Ozone-Induced Systemic Leukocyte Trafficking and Adrenal-Derived Stress Hormones. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 458(152823): 1, (2021).

This dataset includes data for the manuscript in progress, Intracerebroventricular kynurenic acid modulation differentially regulates the immune and neuroendocrine stress response to acute ozone exposure. This study employed the use of kynurenic acid or the kynurenic acid synthesis inhibitor, PF-04859989 infused into the dorsal third ventricle of the brain in male WKY rats, prior to acute ozone exposure at 0.8 ppm, to evaluate the role of kynurenic acid in modulating the neuroendocrine stress response to ozone. Our results indicate that kynurenic acid may have a protective role in the brain, in attenuating the pulmonary and systemic effects of ozone exposure, perhaps through multiple mechanisms. This dataset is associated with the following publication: Rentschler, K., M.C. Schladweiler, R. Grindstaff, W. Williams, P.R. Kodavanti, D. Freeborn, L. Klein, G. Jung, D. Herr, P. Evansky, J. McKee, S. Gavett, and U. Kodavanti. Differential Effects of Intracerebroventricular Kynurenic Acid Regulation on the Inflammatory and Neuroendocrine Response to Acute Ozone Exposure. Presented at Society of Toxicology, Orlando, FL, USA, 03/16/2025 - 03/20/2025.

This data set shows high throughput gene expression assessment using RNAseq to examine how ozone-induced transcriptional changes in the lung are influenced by adrenalectomy or adrenal demedullation in rats. We have previously observed that lung injury and inflammation are diminished in adrenalectomized rats and this study was planned to understand if circulating stress hormones influence ozone transcriptional effects and what ozone-induced pathway changes might be impacted by removal of adrenal glands. This dataset is associated with the following publication: Henriquez, A., J. House, D. Miller, S. Snow, A. Fisher, H. Ren, M. Schladweiler, A. Ledbetter, F. Wright, and U. Kodavanti. Adrenal-derived stress hormones modulate ozone-induced lung injury and inflammation. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, USA, 329: 249-258, (2017).

Objective: Inhalation of ozone activates central sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal stress axes. While airway neural networks are known to communicate noxious stimuli to higher brain centers, it is not known to what extent responses generated from pulmonary airways contribute to neuroendocrine activation. Materials and methods: Unlike inhalational exposures that involve the entire respiratory tract, we employed intratracheal (IT) instillations to expose only pulmonary airways to either soluble metal-rich residual oil fly ash (ROFA) or compressor-generated diesel exhaust particles (C-DEP). Male Wistar-Kyoto rats (12-13 weeks) were IT instilled with either saline, C-DEP or ROFA (5 mg/kg) and necropsied at 4 or 24 hr to assess temporal effects. Results: IT-instillation of particulate matter (PM) induced hyperglycemia as early as 30-min and glucose intolerance when measured at 2 hr post-exposure. We observed PM- and time-specific effects on markers of pulmonary injury/inflammation (ROFA>C-DEP; 24 hr>4hr) as corroborated by increases in lavage fluid injury markers, neutrophils (ROFA>C-DEP), and lymphocytes (ROFA). Increases in lavage fluid pro-inflammatory cytokines differed between C-DEP and ROFA in that C-DEP caused larger increases in TNF-α whereas ROFA caused larger increases in IL-6. No increases in circulating cytokines occurred. At 4 hr, PM impacts on neuroendocrine activation were observed through depletion of circulating leukocytes, increases in adrenaline (ROFA), and decreases in thyroid-stimulating-hormone, T3, prolactin, luteinizing-hormone, and testosterone. C-DEP and ROFA both increased lung expression of genes involved in acute stress and inflammatory processes. Moreover, small increases occurred in hypothalamic Fkbp5, a glucocorticoid-sensitive gene. Conclusion: Respiratory alterations differed between C-DEP and ROFA, with ROFA inducing greater overall lung injury/inflammation; however, both PM induced a similar degree of neuroendocrine activation. These findings demonstrate neuroendocrine activation after pulmonary-only PM exposure, and suggest the involvement of pituitary- and adrenal-derived hormones. This dataset is associated with the following publication: Alewel, D., A. Henriquez, M. Schladweiler, R. Grindstaff, A. Astriab Fisher, S. Snow , T. Jackson, and U. Kodavanti. Intratracheal instillation of respirable particulate matter elicits neuroendocrine activation. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, USA, 35(3-4): 59-75, (2023).

The dataset is comprised of multiple data-frames. Our focus is on sex and brain region specific responses to ozone in a rat model. The PCR data describes the gene expression from listed brain regions resulting from ozone exposure. Complex enzymes were also assayed due to their sensitivity to oxidative stress using biochemical colorimetric assays. And finally, we collected data for oxidative stress artifacts such as protein carbonyl productions, total antioxidants, and enzyme activity. This dataset is associated with the following publication: Valdez, M., D. Freeborn, P. Vulimiri, J. Valdez, U. Kodavanti, and P. Kodavanti. Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus are Sex-Specific.. International Journal of Molecular Sciences. MDPI, Basel, SWITZERLAND, 24(7): 1, (2023).

The dataset is comprised of multiple data-frames. Our focus is on sex and brain region specific responses to ozone in a rat model. The PCR data describes the gene expression from listed brain regions resulting from ozone exposure. Complex enzymes were also assayed due to their sensitivity to oxidative stress using biochemical colorimetric assays. And finally, we collected data for oxidative stress artifacts such as protein carbonyl productions, total antioxidants, and enzyme activity. This dataset is associated with the following publication: Valdez, M., D. Freeborn, P. Vulimiri, J. Valdez, U. Kodavanti, and P. Kodavanti. Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus are Sex-Specific.. International Journal of Molecular Sciences. MDPI, Basel, SWITZERLAND, 24(7): 1, (2023).