Air pollution is associated with brainstem auditory nuclei pathology and delayed brainstem auditory evoked potentials

Abstract

We assessed brainstem inflammation in children exposed to air pollutants by comparing brainstem auditory evoked potentials (BAEPs) and blood inflammatory markers in children age 96.3± 8.5 months from highly polluted (n=34) versus a low polluted city (n=17). The brainstems of nine children with accidental deaths were also examined. Children from the highly polluted environment had significant delays in wave III (t(50)=17.038; p<0.0001) and wave V (t(50)=19.730; p<0.0001) but no delay in wave I (p=0.548). They also had significantly longer latencies than controls for interwave intervals I–III, III–V, and I–V (all t(50)> 7.501; p<0.0001), consisting with delayed central conduction time of brainstem neural transmission. Highly exposed children showed significant evidence of inflammatory markers and their auditory and vestibular nuclei accumulated α synuclein and/or β amyloid 1–42. Medial superior olive neurons, critically involved in BAEPs, displayed significant pathology. Children’s exposure to urban air pollution increases their risk for auditory and vestibular impairment.

Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution

“…Moreover, under experimental conditions, exposures to different components of air pollutants cause oxidative stress, neuroinflammation and neurodegeneration (Calderón-Garcidueñas et al, 2003, 2008a, 2012a,b; Levesque et al, 2011, 2013). Thus, the CSF and brain inflammatory imbalance observed in highly exposed children could represent an early physiological reaction to chronic environmental stress contributing later to the establishment of neurodegenerative processes with childhood clinical manifestations (Calderón-Garcidueñas et al, 2008b, 2011b, 2012b, 2013). Of critical importance are the portals of entry of air pollutants in the urban setting: (i) the nasal pathway through the olfactory, trigeminal nerves and accessory posterolateral nerve, (ii) the red blood cells and monocytes transporting ultrafine PM and then delivering the particles to distant organs including the brain, (iii) the direct access of PM organic and inorganic components to the systemic circulation through the alveolar-capillary interphase, (iv) the gastrointestinal and vagal pathways (Calderón-Garcidueñas et al, 2007; Block and Calderón-Garcidueñas, 2009; Dhuria et al, 2010; Bleier et al, 2012; Lucchini et al, 2012).…”

“…We already described some of these consequences in Mexico City youth: differences in white matter volumes involving right parietal and bilateral temporal areas and cognitive deficits consistent with impairment of the targeted lobes, olfaction deficits, auditory and vestibular nuclei accumulating α synuclein and/or β amyloid and significant involvement of the medial superior olive neurons, critically involved in brainstem auditory evoked potentials. Elevation of indices of neuroinflammation and oxidative stress, and AD and PD associated pathology completing the grim picture (Calderón-Garcidueñas et al, 2003, 2008a,b, 2010, 2011a,b, 2012a,b, 2013; Calderón-Garcidueñas and Torres-Jardón, 2012). …”

“…The complex modulation of cytokines and chemokines that influence children's central nervous system (CNS) structural and volumetric responses to air pollution obligate the search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term (Calderón-Garcidueñas et al, 2008a,b, 2011a,b, 2012b). A good candidate biomarker, macrophage migration inhibitory factor (MIF) is a cytokine expressed in the CNS and involved in innate and adaptive immune responses (Bernhagen et al, 1993; Bacher et al, 2010; Edwards et al, 2010; Moon et al, 2012; Savaskan et al, 2012; Bucala, 2013; Cox et al, 2013; Freiria-Oliveira et al, 2013; Turtzo et al, 2013).…”

Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond

“…Misfolded α-synuclein is present in 23.5% of < 25 y MC residents [66] and the brainstem distribution of this protein follows key anatomical regions known to be involved early in Parkinson's disease (PD) stages [67,68]. Specifically, α-synuclein has been observed in the dorsal vagal nucleus, solitary complex, lower raphe nuclei, locus coeruleus and pedunculo-pontine nuclei, as well as in the olfactory bulb of young MC residents [34,66]. These findings correspond to Braak stages I and II of PD characterized by autonomic and olfactory disturbances [67][68][69], that are indeed present in our exposed pediatric cohorts [66].…”

“…Specifically, α-synuclein has been observed in the dorsal vagal nucleus, solitary complex, lower raphe nuclei, locus coeruleus and pedunculo-pontine nuclei, as well as in the olfactory bulb of young MC residents [34,66]. These findings correspond to Braak stages I and II of PD characterized by autonomic and olfactory disturbances [67][68][69], that are indeed present in our exposed pediatric cohorts [66]. Our observations put forward a key question raised by numerous researchers: What events trigger the onset of Parkinson's disease?…”