Degeneration and regeneration of the olfactory epithelium following inhalation exposure to methyl bromide: Pathology, cell kinetics, and olfactory function

Hurtt, Mark E.; Thomas, Deborah A.; Monticello, Thomas M.; Morgan, Kevin T.

doi:10.1016/0041-008x(88)90273-6

Cited by 134 publications

(58 citation statements)

References 35 publications

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“…On the one hand, that capacity underlies the ability of the system to recover anatomically after injury, as documented previously in numerous studies by numerous investigators (for review, see Graziadei and Monti Graziadei, 1985;Costanzo, 1991;Schwob, 2002). For example, passive inhalation of the selective olfactotoxin methyl bromide (MeBr) destroys olfactory sensory neurons (OSNs) and sustentacular cells in Ͼ95% of the olfactory epithelium (OE) (Hurtt et al, 1987(Hurtt et al, , 1988Schwob et al, 1995Schwob et al, , 1999. Despite the severity of the initial lesion, the OE begins to reconstitute within a few days after lesion and has recovered to normal by 6 weeks with respect to the rate of neuronal turnover and the balance between mature and immature OSNs .…”

Section: Introductionmentioning

confidence: 96%

“…Previous descriptions of the acute effects of MeBr exposure and the reconstitution of the OE over the long term have concentrated on animals exposed bilaterally to the toxin (Hurtt et al, 1988;Schwob et al, 1995Schwob et al, , 1999. To take advantage of the potential for a within-animal control, we modified the procedure to limit effective exposure to one side of the OE by closing the left naris of rats maintained on chronic food restriction.…”

Section: Or Expression Is Eliminated Shortly After Unilateral Mebr Exmentioning

confidence: 99%

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Odorant Receptor Expression Patterns Are Restored in Lesion-Recovered Rat Olfactory Epithelium

Iwema¹,

Fang²,

Kurtz³

et al. 2004

J. Neurosci.

133

112

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Lesions of the olfactory periphery provide a means for examining the reconstitution of a diverse and highly regulated population of sensory neurons and the growth, en masse, of nascent axons to the bulb. The olfactory epithelium and its projection onto the bulb are reconstituted after ablation by methyl bromide gas, and some measure of olfactory function is restored. The extent to which the system regenerates the full repertoire of odorant receptor-expressing neurons, particularly their spatially restricted distribution across the epithelial sheet, is unknown, however, and altered odorant receptor expression might contribute to the persistent distortion of odorant quality that is observed in the lesioned-recovered animals. To address the question of receptor expression in the recovered epithelium, we performed in situ hybridization with digoxigenin-labeled riboprobes for eight odorant receptors on the olfactory epithelium from unilaterally methyl bromide-lesioned and control rats. The data demonstrate that the distribution of sensory neuron types, as identified and defined by odorant receptor expression, is restored to normal or nearly so by 3 months after lesion. Likewise, the numbers of probe-labeled neurons in the lesioned-recovered epithelium are nearly equivalent to the unlesioned side at this time. Finally, our evidence suggests that odorant receptors are distributed in multiple overlapping bands in the normal, unlesioned, and lesioned-recovered epithelium rather than in the conventionally accepted three or four zones. Thus, the primary sensory elements required for functional recovery of the olfactory system after damage are restored, and altered function implies the persistence of a more central failure in regeneration.

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Section: Introductionmentioning

confidence: 96%

Section: Or Expression Is Eliminated Shortly After Unilateral Mebr Exmentioning

confidence: 99%

Odorant Receptor Expression Patterns Are Restored in Lesion-Recovered Rat Olfactory Epithelium

Iwema¹,

Fang²,

Kurtz³

et al. 2004

J. Neurosci.

133

112

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“…Following inhalation or intranasal instillation of nasal toxicants an increased rate of cell replication has been reported in the olfactory neuroepithelium (16,29). The present studies showed that systemic administration of dichlobenil induced a dose-dependent increase in the rate of cell replication in the lamina propria, whereas the rate of cell replication in the neuroepithelium was only increased at the highest dose (25 mg/kg).…”

Section: Vehicle-treated Mice and Untreated Mice Light Microscopy Andmentioning

confidence: 99%

Effects of Dichlobenil on Ultrastructural Morphology and Cell Replication in the Mouse Olfactory Mucosa

1997

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The herbicide dichlobenil (2,6-dichlorobenzonitrile) is a tissue-specific toxicant inducing necrosis in the olfactory mucosa. Transmission electron microscopy showed vacuolations (1 hr) and necrosis (4 hr) in the Bowman's glands following intraperitoneal injection of dichlobenil (25 mg/kg) in C57B1 mice, whereas no lesions were noted in the olfactory neuroepithelium at these timepoints. Twentyfour hr following injection (25 mg/kg), most of the lamina propria and the olfactory epithelium were severely damaged; the basal lamina, nerves, and blood vessels in the lamina propria, however, remained intact. Following a lower dose (12 mg/kg), the lesions were not as pronounced. The effects of dichlobenil (6, 12, and 25 mg/kg) on cell replication in the olfactory mucosa, as determined by incorporation of 3H-thymidine 3 days later, were more pronounced in the lamina propria than in the neuroepithelium and occurred at a lower dose in the lamina propria than in the neuroepithelium. Together these studies support the previous proposal that dichlobenil induces a primary damage in the Bowman's glands.

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“…A rapid burst of basal cell proliferation occurs over the next few days, and the epithelium gradually regenerates during the next 4-8 weeks during which time olfactory epithelial cell proliferation declines toward control values (12). The sampling site selected for the present olfactory epithelial studies was the 2' ectoturbinate ( Fig.…”

Section: Determination Of Cell Proliferationmentioning

confidence: 99%

“…The material used for this work was derived from a previous study reported by Hurtt et al (12). Histoautoradiography was used to assess olfactory epithelial cell kinetics during and following acute inhalation exposure of male F-344 rats to methyl bromide (MeBr).…”

Section: Cell Proliferation Studies Of Olfactory Epitheliummentioning

confidence: 99%

Unit Length as the Denominator for Quantitation of Cell Proliferation in Nasal Epithelia

1990

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Cell proliferation data, generally based on a labeling index (LI), provide a valuable endpoint for assessment of toxic and potentially carcinogenic responses in laboratory animals. Measurement of the LI is time consuming because of the large number of cells that need to be counted to determine the denominator. In respiratory mucosa, the total cell count of the surface epithelia may be altered in response to treatment, either through cell loss or increases in cell number (e.g., hyperplasia). As an alternative to the more conventional LI, the present studies were carried out to assess the value of expressing cell proliferation in nasal epithelia as a unit length labeling index (ULLI), defined as labeled cells per mm of basement membrane. Rats were exposed by inhalation to formaldehyde or methyl bromide, and changes in cell proliferation were determined in the respiratory and olfactory epithelia, respectively, using both total cell count and basement membrane length as denominators. Total cell counts were clearly influenced by treatment, while basement membrane length was not. Both methods revealed similar treatment-induced effects on cell proliferation, and in fact were highly correlated (R 2: 0.92, p < 0.001). It was concluded that the ULLI method provides an effectivealternative to total cell counts and the LI method. This approach is not influenced by alterations in the total cell population, and has the benefit of being less labor intensive than LI determinations.

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Degeneration and regeneration of the olfactory epithelium following inhalation exposure to methyl bromide: Pathology, cell kinetics, and olfactory function

Cited by 134 publications

References 35 publications

Odorant Receptor Expression Patterns Are Restored in Lesion-Recovered Rat Olfactory Epithelium

Odorant Receptor Expression Patterns Are Restored in Lesion-Recovered Rat Olfactory Epithelium

Effects of Dichlobenil on Ultrastructural Morphology and Cell Replication in the Mouse Olfactory Mucosa

Unit Length as the Denominator for Quantitation of Cell Proliferation in Nasal Epithelia

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