World Trade Center dust induces nasal and neurological tissue injury while propagating reduced olfaction capabilities and increased anxiety behaviors.

Previous and in vivo World Trade Center particulate matter (WTC) exposure studies have provided evidence of exposure-driven oxidative/nitrative stress and inflammation on respiratory tract and aortic tissues. What remains to be fully understood are secondary organ impacts due to WTC exposure. This study was designed to test if WTC particle-induced nasal and neurologic tissue injury may result in unforeseen functional and behavioral outcomes. WTC was intranasally administered in mice, evaluating genotypic, histopathologic, and olfaction latency endpoints. WTC exposure was found to incite neurologic injury and olfaction latency in intranasally (IN) exposed mice. Single high-dose and repeat low-dose nasal cavity insults from WTC dust resulted in significant olfaction delays and enduring olfaction deficits. Anxiety-dependent behaviors also occurred in mice experiencing olfaction loss including significant body weight loss, increased incidence and time spent in hind stretch postures, as well as increased stationary time and decreased exploratory time. Additionally, WTC exposure resulted in increased whole brain wet/dry ratios and wet whole brain to body mass ratios that were correlated with exposure and increased exposure dose (<0.05). The potential molecular drivers of WTC-driven tissue injury and olfaction latency may be linked to oxidative/nitrative stress and inflammatory cascades in both upper respiratory nasal and brain tissues. Cumulatively, these data provide evidence of WTC exposure in relation to tissue damage related to oxidative stress-driven inflammation identified in the nasal cavity, propagated to olfactory bulb tissues and, potentially, over extended periods, to other CNS tissues.