C. Children and young adults living in Mexico City
Additional evidence for the role of particles and associated toxins as causation in the onset of toxic encephalopathy is derived from observations of children and young adults residing in Mexico City. Particulate matter in polluted outdoor air consists of fine and ultrafine particles to which toxins are adsorbed.
Autopsies were performed on children and young adults who had died suddenly and who did not have familial or personal history of neurological disease. Inhaled particles were observed by electron and light microscopy. They were distributed to organs (liver, spleen, kidneys, brain, within RBCs and heart) via the systemic circulation and/or by macrophage and dendritic cell activity and via the olfactory mucosa.
Observations on the brains showed marked up-regulation of inflammatory markers in the frontal cortex, olfactory bulb, substantia nigrae, vagus nerve and disruption of the blood brain barrier. Pathological observations included deposition of ultrafine particles, accumulation of amyloid beta-42, alpha synuclein and increase of expression of COX2 in the brains.
These findings were observed in the frontal cortex, olfactory bulb, substantia nigrae and vagus nerve of affected individuals (Peters et al, 2006; Calderon-Garciduenas et al, 2004, 2007, 2008a-c). The pathology resembled that of Alzheimer- and Parkinson-like diseases (Calderon-Garciduenas et al, 2004; 2008a).
Clinically healthy children exposed to air pollutants have systemic inflammation and endothelial damage with significant increases in inflammatory markers (TNF-alpha, PGE2, C- reactive protein, IL-1beta, endothelin-1) with a concomitant down-regulation of soluble adhesion molecules (Calderon-Garciduenas et al, 2008b).
Finally, exposed children exhibited significant deficits in short- and long-term cognition with neuropsychological testing. Over 50% of them had MRI findings of prefrontal white matter hyperintense lesions. Concomitantly exposed canines had the same MRI changes and increases in COX2 inflammatory markers, i.e., neuroinflammation (Calderon-Garciduenas et al, 2008c; Block and Calderon-Garciduenas).
In conclusion, published observations point toward the role of fine particles in the exposure of occupants in water-damaged structures to mycotoxins and other biocontaminants.
The observations include:
1) particulates <1.5 um contain trichothecenes and are associated with growth of the mold (Brasel et al, 2005a,b);
2) the trichothecenes were detected in the sera of symptomatic individuals occupying the S. chartarum contaminated structures (Brasel, et al, 2004);
3) trichothecenes and other mold by-products are present in particles <2 um in other settings and are cytotoxic in the MTT assay (Johanning et aI, 2002);
4) trichothecenes are in the urine, blood, nasal and lung secretions of individuals exposed to molds in water-damaged homes (Croft et al, 1986; 2002; Hooper et al, 2009);
5) Finally, the blood concentrations of the hemolytic protein (stachylysin) of five symptomatic individuals exposed to S.chartarum averaged 371 nanograms/ml (Van Emon et al, 2003); and
6) Toxic strains of Bacilli, Nocardia and Streptomyces were isolated from indoor air in the particle range of 0.56 to 2.1 microns (Peltola, et al, 2001a, b).
Block ML, Calderon-Garciduenas L. 2009. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci 32:506-16.
Brasel TL, Campbell AW, Demers RE, Ferguson BS, Fink J, Vojdani A, Wilson SC, Straus DC. 2004. Detection of trichothecene mycotoxins in sera from individuals exposed to Stachybotrys chartarum in indoor environments. Arch Environ Health 59:417-23.
Brasel TL, Martin JM, Carriker CG, Wilson SC Straus DC. 2005. Detection of airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins in indoor environment. Appl Environ Microbiol 71:7376-88.
Brasel TL, Douglas DR, Wilson SC, Straus DC. 2005. Detection of airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins on particulates smaller than conidia. 71:114-22.
Calderon-Garciduenas L, Reed W, Maronpot RR, Henriquez-Roldan C, Delgado-Chavez R, Calderón-Garcidueñas A, Dragustinovis I, Franco-Lira M, et al. 2004. Brain inflammation and Alzheimer’s-like pathology in individuals exposed to severe air pollution. Toxicol Pathol 32:650-8.
Calderon-Garciduenas L, Franco-Lira M, Toress-Jardo R, Henriquez-Rodan C, et al. 2007. Pediatric respiratory and systemic effects of chronic air pollution exposure: Nose, lung, heart and brain pathology. Toxicol Pathol 35:154-62.
Calderon-Garciduenas L, Solt AC, Henriquez-Roldan C, Torres-Jardon, R, Nuse B, Herritt L, Villarreal-Calderón R, et al. 2008. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults. Toxicol Pathol 26:289-310.
Calderon-Garciduenas L, Villarreal-Calderon R, Valencia-Salazar G, Henriquez-Roldan C, Gutiérrez-Castrellón P, Torres-Jardón R, et al. 2008. Systemic inflammation, endothelial dysfunction, and activation in healthy children exposed to air pollution. Inhal Toxicol 20-499-506.
Calderon-Garciduenas L, Mora-Tiscareno A, Ontiveros E, Gomez-Garza G, Barragan-Mejia G, Guillé B, Torres-Jardón R, et al. 2008. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cognition 68: 117-27.
Johanning E, Gareis M, Nielsen K, Dietrich R, Martlbauer E. 2002. Airborne mycotoxins sampling and screening analysis. Proceedings of the 9th International Conference on Indoor Air Quality and Climate (Indoor Air), Monterey, CA, June 20-July 5.
Croft WA, Jarvis BB. Yatawara CS. 1986. Airborne outbreak of trichothecene toxicosis. Atmosphere Environ 20:549-52.
Croft WA, Jastromiski BM, Croft AL, Peters HA. 2002. Clinical confirmation of trichothecene mycotoxicosis in patient urine. J Environ Biol 23:301-20.
Peltola JSP, Andersson MA, Haahtela T, Mussalo-Rauhamaa J, Rainey F, Kroppenstedt RM, Samson RA, Salkinoja-Salonen MS. 2001. Toxic metabolite producing bacteria and fungus in an indoor environment. Appl Environ Microbiol 67:3269-74.
Peltola JSP, Andersson MA, Kamper P, Auling G, Kroppenstedt RM, Busse HJ, Salkinoja-Salonen MS, Rainey FA. 2001. Isolation of toxigenic Nocardiopsis strains from indoor environments and description of two new Nocardiopsis species, N. exhalans sp. novo and N. umidischolae sp. novo. Appl Environ Microbiol 67:4293-4304.
Peters A, Verones B, Calderon-Garciduenas L, Gehr P, Chen LC, et al. 2006. Translocation and potential neurological effects of fine and ultrafine particles: a critical update. Part Fibre Toxicol 3:13-25.
Van Emon, JM, Reed AW, Yike I, Vesper SJ. 2003. ELISA measurement of stachylysin in serum to quantify human exposures to indoor mold Stachybotrys chartarum. J Occup Environ Med 45:582-91.
D. Chronic Inflammation of the Brain
It is becoming increasingly apparent that chronic inflammation of the brain is associated with a variety of neurological conditions. These include Multiple Sclerosis, Parkinson's Disease, Alzheimer's, Limbic Encephalitis, Neurocognitive deficits and neuropsychiatric conditions, among others. The inflammation results from both systemic and centrally produced pro-inflammatory cytokines and chemokines.
Microglia are immune cells that are present within the brain and the spinal cord. These cells can become hyperactivated and release cytokines and chemokines that result in inflammatory damage to myelin and cell death of neurons.