OLFATO: forma más antigua de comunicación y sentido preciso que el otorrinolaringólogo debe conocer a profundidad / SMELL: oldest form of communication and precise sense that the otolaryngologist must know in depth

Introducción: el papel clave del olfato, antiguo sistema sensorial, es proporcionar información sobre las sustancias químicas en el medio ambiente. El olfato desempeña un papel en la detección de compuestos peligrosos, el mantenimiento de la nutrición, el comportamiento interpersonal, la salud neurológica y la sensación de placer, entre otras funciones. En consecuencia, la disfunción olfativa puede conducir a un riesgo de lesiones, desnutrición, aislamiento social y una mala calidad de vida. Materiales y métodos: se realizó una exploración bibliográfica y se identificaron artículos de acuerdo con los criterios de inclusión y exclusión definidos y se tomaron aquellos con calidad en la evidencia. Discusión: el sistema olfativo humano tiene diferencias anatómicas, fisiológicas y genéticas considerables con respecto al de otros mamíferos. Conclusiones: las destrezas olfativas varían con factores como la edad, el sexo, la etapa de desarrollo, ciertas enfermedades otorrinolaringológicas y enfermedades generales.

Introduction: The key role of the ancient olfactory sensory system is to provide information about chemicals in the environment. Smell plays a role in the detection of dangerous compounds, the maintenance of nutrition, interpersonal behavior, neurological health, and the sensation of pleasure, among other functions. Consequently, olfactory dysfunction can lead to a risk of injury, malnutrition, social isolation, and a poor quality of life. Materials and methods: A bibliographical exploration was carried out and articles were identified according to the inclusion and exclusion criteria defined and those with quality evidence were taken. Discussion: The human olfactory system has considerable anatomical, physiological, and genetic differences from that of other mammals. Conclusions: Olfactory skills vary with factors such as age, sex, stage of development, certain ear, nose and throat diseases and general diseases.

Frequency-dependent centrifugal modulation of the activity of different classes of mitral and tufted cells in olfactory bulb.

Mitral/tufted cells (M/TCs), the principal output neuron classes form complex circuits with bulbar neurons and long-range centrifugal circuits with higher processing areas such as the horizontal limb of the diagonal band of Broca (HDB). The precise excitability of output neurons is sculpted by local inhibitory circuits. Here, light-gated cation channel channelrhodopsin-2 (ChR2) was expressed in HDB GABAergic neurons to investigate the short-term plasticity of evoked postsynaptic currents/potentials of HDB input to all classes of M/TCs and effects on firing in the acute slice preparation. Activation of the HDB directly inhibited all classes of output neurons exhibiting frequency-dependent short-term depression of evoked inhibitory postsynaptic current (eIPSC)/potential (eIPSP), resulting in decreased inhibition of responses to olfactory nerve input as a function of input frequency. In contrast, activation of an indirect circuit of HDB→interneurons→M/TCs induced frequency-dependent disinhibition, resulting in short-term facilitation of evoked excitatory postsynaptic current (eEPSC) eliciting a burst or cluster of spiking in M/TCs. The facilitatory effects of elevated HDB input frequency were strongest on deeper output neurons (deep tufted and mitral cells) and negligible on peripheral output neurons (external and superficial tufted cells). Taken together, GABAergic HDB activation generates frequency-dependent regulation that differentially affects the excitability and responses across the five classes of M/TCs. This regulation may help maintain the precise balance between inhibition and excitation of neuronal circuits across the populations of output neurons in the face of changes in an animal sniffing rate, putatively to enhance and sharpen the tuning specificity of individual or classes of M/TCs to odors.NEW & NOTEWORTHY Neuronal circuits in the olfactory bulb closely modulate olfactory bulb output activity. Activation of GABAergic circuits from the HDB to the olfactory bulb has both direct and indirect action differentially across the five classes of M/TC bulbar output neurons. The net effect enhances the excitability of deeper output neurons as HDB frequency increases, altering the relative inhibition-excitation balance of output circuits. We hypothesize that this sharpens the tuning specificity of classes of M/TCs to odors during sensory processing.

Open pathways for cerebrospinal fluid outflow at the cribriform plate along the olfactory nerves.

BACKGROUND: Routes along the olfactory nerves crossing the cribriform plate that extend to lymphatic vessels within the nasal cavity have been identified as a critical cerebrospinal fluid (CSF) outflow pathway. However, it is still unclear how the efflux pathways along the nerves connect to lymphatic vessels or if any functional barriers are present at this site. The aim of this study was to anatomically define the connections between the subarachnoid space and the lymphatic system at the cribriform plate in mice. METHODS: PEGylated fluorescent microbeads were infused into the CSF space in Prox1-GFP reporter mice and decalcification histology was utilized to investigate the anatomical connections between the subarachnoid space and the lymphatic vessels in the nasal submucosa. A fluorescently-labelled antibody marking vascular endothelium was injected into the cisterna magna to demonstrate the functionality of the lymphatic vessels in the olfactory region. Finally, we performed immunostaining to study the distribution of the arachnoid barrier at the cribriform plate region. FINDINGS: We identified that there are open and direct connections from the subarachnoid space to lymphatic vessels enwrapping the olfactory nerves as they cross the cribriform plate towards the nasal submucosa. Furthermore, lymphatic vessels adjacent to the olfactory bulbs form a continuous network that is functionally connected to lymphatics in the nasal submucosa. Immunostainings revealed a discontinuous distribution of the arachnoid barrier at the olfactory region of the mouse. INTERPRETATION: Our data supports a direct bulk flow mechanism through the cribriform plate allowing CSF drainage into nasal submucosal lymphatics in mice. FUNDING: This study was supported by the Swiss National Science Foundation (310030_189226), Dementia Research Switzerland-Synapsis Foundation, the Heidi Seiler Stiftung and the Fondation Dr. Corinne Schuler.

Impact of trigeminal nerve and/or olfactory nerve stimulation on activity of human brain regions involved in the perception of breathlessness.

Breathlessness is a centrally processed symptom, as evidenced by activation of distinct brain regions such as the insular cortex and amygdala, during the anticipation and/or perception of breathlessness. Inhaled L-menthol or blowing cool air to the face/nose, both selective trigeminal nerve (TGN) stimulants, relieve breathlessness without concurrent improvements in physiological outcomes (e.g., breathing pattern), suggesting a possible but hitherto unexplored central mechanism of action. Four databases were searched to identify published reports supporting a link between TGN stimulation and activation of brain regions involved in the anticipation and/or perception of breathlessness. The collective results of the 29 studies demonstrated that TGN stimulation activated 12 brain regions widely implicated in the anticipation and/or perception of breathlessness, including the insular cortex and amygdala. Inhaled L-menthol or cool air to the face activated 75% and 33% of these 12 brain regions, respectively. Our findings support the hypothesis that TGN stimulation contributes to breathlessness relief by altering the activity of brain regions involved in its central neural processing.

Impact of trigeminal and/or olfactory nerve stimulation on measures of inspiratory neural drive: Implications for breathlessness.

The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on the trigeminal nerve (TGN) with TGN agonists such as menthol or cool air to the face/nose has been hypothesized to reduce breathlessness by decreasing IND. The aim of this systematic scoping review was to identify and summarize the results of studies in animals and humans reporting on the impact of TGN stimulation or blockade on measures of IND. Thirty-one studies were identified, including 19 in laboratory animals and 12 in human participants. Studies in laboratory animals consistently reported that as TGN activity increased, measures of IND decreased (e.g., phrenic nerve activity). In humans, stimulation of the TGN with a stream of cool air to the face/nose decreased the sensitivity of the ventilatory chemoreflex response to hypercapnia. Otherwise, TGN stimulation with menthol or cool air to the face/note had no effect on measures of IND in humans. This review provides new insight into a potential neural mechanism of breathlessness relief with selected TGN agonists.

Wide-ranging migration and destination of early olfactory placode-derived neurons in chick embryos.

Cell migration from the olfactory placode (OP) is a well-known phenomenon wherein various cell types, such as gonadotropin-releasing hormone (GnRH)-producing neurons, migrate toward the telencephalon (TEL) during early embryonic development. However, the spatial relationship between early migratory cells and the forebrain is unclear. We examined the early development of whole-mount chick embryos to observe the three-dimensional spatial relationship among OP-derived migratory neurons, olfactory nerve (ON), and TEL. Migratory neurons that express highly polysialylated neural cell adhesion molecule (PSA-NCAM) emerge from the OP and spread over a relatively wide TEL area at the Hamburger and Hamilton (HH) stage 17. Most migratory neurons form a cellular cord between the olfactory pit and rostral TEL within HH18-20. The earliest axons from the olfactory epithelium (OE) were detected along this neuronal cord using DiI-labeling at HH21. Furthermore, a few PSA-NCAM-positive neurons were dispersed around the cellular cord and over the lateral TEL at HH18. A long cellular cord branch extending to the lateral TEL was transiently observed within HH18-24. These results suggest a novel migratory route of OP-derived neurons during the early developmental stages. Following GFP vector introduction into the OP of HH13-15 embryos, labeled neurons were detected around and within the lateral TEL at HH23 and HH27. At HH36, labeled cells were observed in the rostral-lateral TEL, including the olfactory bulb (OB) region. GFP-labeled and calretinin-positive neurons were detected in the OB, suggesting that early OP-derived neurons enter the forebrain and function as interneurons in the OB.

Rapid presynaptic maturation in naturally regenerating axons of the adult mouse olfactory nerve.

Successful neuronal regeneration requires the reestablishment of synaptic connectivity. This process requires the reconstitution of presynaptic neurotransmitter release, which we investigate here in a model of entirely natural regeneration. After toxin-induced injury, olfactory sensory neurons in the adult mouse olfactory epithelium can regenerate fully, sending axons via the olfactory nerve to reestablish synaptic contact with postsynaptic partners in the olfactory bulb. Using electrophysiological recordings in acute slices, we find that, after initial recontact, functional connectivity in this system is rapidly established. Reconnecting presynaptic terminals have almost mature functional properties, including high release probability and strong capacity for presynaptic inhibition. Release probability then matures quickly, rendering reestablished terminals functionally indistinguishable from controls just 1 week after initial contact. These data show that successful synaptic regeneration in the adult mammalian brain is almost a "plug-and-play" process, with presynaptic terminals undergoing a rapid phase of functional maturation as they reintegrate into target networks.

The Olfactory Nerve: Anatomy and Pathology.

The human sense of smell is the unique sense through which the olfactory system can identify aromatic molecules within the air and provide a taste sensation. Still, also it plays an essential role in several other functions, warning about environmental safety and even impacts our emotional lives. Recently, olfactory impairment has become an issue of interest due to the COVID-19 pandemic. The dysfunction may vary from only reduced smell detection (hyposmia) to complete loss of it (anosmia) but also includes changes in the normal perception of odors (parosmia). Computed tomography and magnetic imaging resonance are the modalities of choice to evaluate the olfactory pathways. Computed tomography is the initial imaging modality for olfactory disturbances, allowing recognition of sinonasal pathologies, inflammatory processes, or bone-related tumors. Magnetic imaging resonance with dedicated protocols for olfactory disorders enables a detailed assessment of the sinonasal compartment and the anterior cranial fossa. Provides a better depiction of olfactory bulb volume, morphology and signal intensity, as well the status of signal intensity of the central olfactory projection areas. Several diseases can affect the olfactory nerve, such as congenital disorders, trauma, inflammatory or infectious diseases, neoplasms, and even post-operative involvement. This article aims to review the normal anatomy of the olfactory nerve pathway and highlight the spectrum of conditions that most commonly affect it.

MRI tractography reveals the human olfactory nerve map connecting the olfactory epithelium and olfactory bulb.

The olfactory nerve map describes the topographical neural connections between the olfactory epithelium in the nasal cavity and the olfactory bulb. Previous studies have constructed the olfactory nerve maps of rodents using histological analyses or transgenic animal models to investigate olfactory nerve pathways. However, the human olfactory nerve map remains unknown. Here, we demonstrate that high-field magnetic resonance imaging and diffusion tensor tractography can be used to visualize olfactory sensory neurons while maintaining their three-dimensional structures. This technique allowed us to evaluate the olfactory sensory neuron projections from the nasal cavities to the olfactory bulbs and visualize the olfactory nerve maps of humans, marmosets and mice. The olfactory nerve maps revealed that the dorsal-ventral and medial-lateral axes were preserved between the olfactory epithelium and olfactory bulb in all three species. Further development of this technique might allow it to be used clinically to facilitate the diagnosis of olfactory dysfunction.

Functional development of olfactory nerve-related neural circuits in the embryonic chick forebrain revealed by voltage-sensitive dye imaging.

Multiple-site optical recordings with NK2761, a voltage-sensitive absorption dye, were applied to the embryonic chick olfactory system, and the functional development of olfactory nerve (N.I)-related neural circuits was examined in the forebrain. The stimulation of the N. I elicited neural responses in N.I-olfactory bulb (OB)-forebrain preparations at the embryonic 8-12 day (E8-E12) stages. At the E11 stage, we functionally identified two circuits projecting from the OB to the forebrain. The first circuit passed through the ventral side of the forebrain and spread in the dorso-caudal direction, whereas the second circuit passed through the dorsal side to the first circuit. Pharmacological experiments showed that N-methyl-D -aspartate (NMDA) receptor function was more significant for the transfer of sensory information in these circuits. The functional development of N.I-related circuits was investigated, and the results obtained revealed that the ventral circuit was generated earlier than the dorsal circuit. Neural responses in the ventral circuit were detected from the E9 stage in normal physiological solution and the E8 stage in Mg2+ -free solution, which activated NMDA receptor function. At the E10 stage, neural responses in the dorsal circuit were clearly recognised in addition to ventral responses. We attempted to identify possible candidates for relay nuclei in the forebrain by comparing contour line maps of the optical signal amplitude with previously reported neuroanatomical data. The results suggest that N.I-related neural circuits from the periphery to the subpallium functionally mature earlier than those to the pallium during ontogenesis.

Olfactory nerve schwannoma: how human anatomy and electron microscopy can help to solve an intriguing scientific puzzle.

Schwannomas of the olfactory nerve are rare tumors: to the best of our knowledge, 56 cases have been previously reported. Here we describe a new patient presenting with an isolated olfactory schwannoma, highlighting the importance of multiple ancillary tests to approach the intracranial lesion of the anterior skull base, including electron microscopy. We also discuss the enigmatic origin of this entity, moving from the normal histology of the olfactory nerve compared to a peripheral nerve.

Olfactory nerve: from ugly duckling to swan.

BACKGROUND: The olfactory nerve has never been the shining star of neurological examination. Quite the contrary, examining the first cranial nerve is often an overlooked step. As cases of anosmia secondary to COVID-19 infection continue to rise, the 2020 pandemic has shed new light on this much-forgotten nerve, its value as an aid to diagnosis of several diseases and its central role in our daily lives. OBJECTIVE: We aimed to emphasize how essential and simple clinical examination of the olfactory system can be by highlighting practical techniques and clinical tips for its assessment. We also share pearls and pitfalls in localization and differential diagnosis, which may prove valuable to busy clinicians. METHODS: A broad review of the literature was conducted by searching PubMed, Cochrane and Google Scholar for articles and books containing topics regarding examination of the olfactory nerve and its anatomy, physiology and pathology. No particular inclusion or exclusion criteria were used. RESULTS: Forty different works were found, between books and articles, from which 20 were selected after careful analysis. CONCLUSIONS: Despite the tragedy and adversity that followed the COVID-19 pandemic, its legacy has taught us a crystal-clear lesson: olfaction should no longer be neglected in clinical practice.

Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer's disease risk.

Chlamydia pneumoniae is a respiratory tract pathogen but can also infect the central nervous system (CNS). Recently, the link between C. pneumoniae CNS infection and late-onset dementia has become increasingly evident. In mice, CNS infection has been shown to occur weeks to months after intranasal inoculation. By isolating live C. pneumoniae from tissues and using immunohistochemistry, we show that C. pneumoniae can infect the olfactory and trigeminal nerves, olfactory bulb and brain within 72 h in mice. C. pneumoniae infection also resulted in dysregulation of key pathways involved in Alzheimer's disease pathogenesis at 7 and 28 days after inoculation. Interestingly, amyloid beta accumulations were also detected adjacent to the C. pneumoniae inclusions in the olfactory system. Furthermore, injury to the nasal epithelium resulted in increased peripheral nerve and olfactory bulb infection, but did not alter general CNS infection. In vitro, C. pneumoniae was able to infect peripheral nerve and CNS glia. In summary, the nerves extending between the nasal cavity and the brain constitute invasion paths by which C. pneumoniae can rapidly invade the CNS likely by surviving in glia and leading to Aß deposition.

Intraoperative Sneezing Secondary to Indirect Olfactory Nerve Stimulation.

Sneezing is a poorly understood, protective reflex response. It's characterized by the following sequence: eye closure, inspiration, glottic closure, forced expiration with sudden glottic opening, and release of an elevated intrathoracic pressure creating a flow of explosive air through the nose.1 Studies have indicated an anatomic sneezing area of the brainstem corresponding to the central recipient zone of the nasal sensory neurons in the lateral medulla.2 The traditional pathophysiology of the sneeze is thought to begin by stimulation of the distal branches of the trigeminal nerve within the nasal mucosa. Afferent neural stimuli are transmitted to the trigeminal ganglion and then the lateral medulla. The efferent phase then begins, giving rise to the sneezing sequence described earlier.1 In addition to direct nasal irritation, sneezing has been shown to be triggered by several other causes (Table 1). This suggests that alternative mechanisms of sneeze induction other than direct nasal stimulation exist. We report a case of a 34-year-old man undergoing an awake craniotomy for a recurrent World Health Organization grade 2 oligodendroglioma (IDH-mutant, 1p19q-codeleted, ATRX preserved). During the operation we elicited a sneeze response on 3 occasions on stimulation of the olfactory nerve (Video 1). Although we cannot completely exclude costimulation of the sensory trigeminal terminations in the anterior fossa floor, the actual sneezing occurred during tumor peeling away from the arachnoid surface overlaying the olfactory nerve. This suggests a potential accessory route of sneeze stimulation involving the olfactory nerve distinct from the previously described trigemino-related, autonomic (sympathetic and parasympathetic systems) and psychogenic etiologies.

Olfactory nerve: from ugly duckling to swan / Nervo olfatório: de patinho feio a cisne

ABSTRACT Background: The olfactory nerve has never been the shining star of neurological examination. Quite the contrary, examining the first cranial nerve is often an overlooked step. As cases of anosmia secondary to COVID-19 infection continue to rise, the 2020 pandemic has shed new light on this much-forgotten nerve, its value as an aid to diagnosis of several diseases and its central role in our daily lives. Objective: We aimed to emphasize how essential and simple clinical examination of the olfactory system can be by highlighting practical techniques and clinical tips for its assessment. We also share pearls and pitfalls in localization and differential diagnosis, which may prove valuable to busy clinicians. Methods: A broad review of the literature was conducted by searching PubMed, Cochrane and Google Scholar for articles and books containing topics regarding examination of the olfactory nerve and its anatomy, physiology and pathology. No particular inclusion or exclusion criteria were used. Results: Forty different works were found, between books and articles, from which 20 were selected after careful analysis. Conclusions: Despite the tragedy and adversity that followed the COVID-19 pandemic, its legacy has taught us a crystal-clear lesson: olfaction should no longer be neglected in clinical practice.

RESUMO Antecedentes: O nervo olfatório nunca foi a estrela do exame neurológico. Pelo contrário, o exame desse nervo craniano é um passo frequentemente ignorado. No entanto, o aumento exponencial de casos de anosmia secundária a COVID-19 o colocou sob os holofotes, tanto em relação á sua função para o ser humano em sociedade, como seu papel no auxílio do diagnóstico de diversas patologias. Objetivos: Enfatizar quão importante é examinar o nervo olfatório e compreender as desordens do seu sistema. Ressaltamos pérolas clínicas e erros comuns no exame deste nervo, além dicas que possam auxiliar no diagnóstico de uma série de doenças neurológicas e sistêmicas. Métodos: Uma ampla revisão da literatura foi conduzida por meio de busca no PubMed, Cochrane e Google Acadêmico por artigos e livros relacionados aos tópicos do exame físico, fisiologia, anatomia e patologia do nervo olfatório. Não foram utilizados critérios específicos de inclusão ou exclusão. Resultados: Foram encontrados 40 artigos itens relacionados na língua inglesa, dentre os quais livros e artigos, tendo sido analisados e selecionados um a um até o total de 20 referências. Conclusões: Apesar da tragédia e adversidade trazidas pela pandemia de COVID-19, uma lição clara permanece: o olfato não deve mais ser negligenciado na prática clínica.

A Comparative Study of Site-Specific Distribution of Aging-Related Tau Astrogliopathy and Its Risk Factors Between Alzheimer Disease and Cognitive Healthy Brains: The Hisayama Study.

Knowledge of aging-related tau astrogliopathy (ARTAG) in healthy elderly individuals remains incomplete and studies to date have not focused on the olfactory nerve, which is a vulnerable site of various neurodegenerative disease pathologies. We performed a semiquantitative evaluation of ARTAG in 110 autopsies in the Japanese general population (Hisayama study). Our analysis focused on Alzheimer disease (AD) and cognitive healthy cases (HC), including primary age-related tauopathy. Among the various diseased and nondiseased brains, ARTAG was frequently observed in the amygdala. The ARTAG of HC was exclusively limited to the amygdala whereas gray matter ARTAG in AD cases was prominent in the putamen and middle frontal gyrus following the amygdala. ARTAG of the olfactory nerve mainly consists of subpial pathology that was milder in the amygdala. A logistic regression analysis revealed that age at death and neurofibrillary tangle Braak stage significantly affected the ARTAG of HC. In AD, age at death and male gender had significant effects on ARTAG. In addition, the Thal phase significantly affected the presence of white matter ARTAG. In conclusion, our research revealed differences in the distribution of ARTAG and affected variables across AD and HC individuals.

Electrophysiological and olfactometric evaluation of long-term COVID-19.

COVID-19 is a public health emergency with cases increasing globally. Its clinical manifestations range from asymptomatic and acute respiratory disease to multiple organ dysfunction syndromes and effects of COVID-19 in the long term. Interestingly, regardless of variant, all COVID-19 share impairment of the sense of smell and taste. We would like to report, as far as we know, the first comprehensive neurophysiological evaluation of the long-term effects of SARS-CoV-2 on the olfactory system with potential-related neurological damage. The case report concerns a military doctor, with a monitored health history, infected in April 2020 by the first wave of the epidemic expansion while on military duty in Codogno (Milan). In this subject, we find the electrophysiological signal in the periphery, while its correlate is absent in the olfactory bulb region than in whole brain recordings. In agreement with this result is the lack of metabolic signs of brain activation under olfactory stimulation. Consequently, quantitative and qualitative diagnoses of anosmia were made by means of olfactometric tests. We strongly suggest a comprehensive series of olfactometric tests from the first sign of COVID-19 and subsequent patient assessments. In conclusion, electrophysiological and metabolic tests of olfactory function have made it possible to study the long-term effects and the establishment of neurological consequences.

Inalação da fumaça do tabaco provoca alterações histopatológicas no nervo olfatório de ratas / Inhalation of tobacco smoke causes histopathological changes in the olfactory nerve of rats

Introdução: o tabagismo é uma das principais causas evitáveis de mortes no mundo representando um problema de saúde pública. Objetivo: investigar a relação da exposição passiva à fumaça principal do cigarro e as possíveis alterações histomorfométricas das células gliais, arteríolas e da matriz extracelular do nervo olfatório de ratas. Metodologia: trata-se de um estudo experimental, analítico e quantitativo. Vinte ratas randomizadas divididas em dois grupos, controle e tabaco, foram expostas à inalação da fumaça principal do cigarro por 60 dias utilizando dispositivo validado na literatura. Resultados: a exposição à inalação da fumaça principal do cigarro resultou em alterações significativas no grupo tabaco, tais como, elevação nos níveis de cotinina no plasma sanguíneo, aumento na espessura da parede dos vasos sanguíneos, aumento na porcentagem do colágeno total do tecido, diminuição no número total de astrócitos e aumento no número total de micróglias. Conclusão: a exposição à fumaça principal do cigarro resulta em alterações histomorfométricas que poderiam causar alterações funcionais no nervo olfatório como perda sensorial olfativa. Os achados constatados são fortes o suficiente para servir como alerta a toda a população e às autoridades de saúde, no que se refere às leis antifumo, principalmente em ambientes fechados.

Introduction: smoking is one of the main preventable causes of death in the world and represents a worldwide public health problem. Objective: to investigate the relationship of second hand tobacco smoke and possible histomorphometric changes of glial cells, arterioles and extracellular matrix of the olfactory nerve in rats. Methodology: experimental, analytical and quantitative study, twenty wistar animals randomized into two control and tobacco groups, were exposed to inhalation of main cigarette smoke for 60 days using a device validated in the literature. Results: exposure to inhalation of main cigarette smoke resulted in changes in the tobacco group, such as increased levels of cotinine in the blood plasma, increased thickness of the blood vessel wall, increased percentage of total tissue collagen, decreased in the total number of astrocytes and increase in the total number of microglia. Conclusion: exposure to main cigarette smoke results in histomorphometric changes that can cause changes in the olfactory nerve such as sensory olfactory loss. Our findings are strong enough to serve as a warning to the entire population and to health authorities in relation to smokefree laws especially in closed environments.