Assessment of Intranasal Function of the Trigeminal Nerve in Daily Clinical Practice.

BACKGROUND: The trigeminal nerve is a mixed cranial nerve responsible for the motor innervation of the masticatory muscles and the sensory innervation of the face, including the nasal cavities. Through its nasal innervation, we perceive sensations, such as cooling, tingling, and burning, while the trigeminal system mediates the perception of airflow. However, the intranasal trigeminal system has received little attention in the clinical evaluation of patients with nasal pathology. SUMMARY: Testing methods that enable the clinical assessment of intranasal trigeminal function have recently been developed. This study aims to present the current clinical methods that can be utilised in everyday practice, as described in the literature. These methods include four assessment techniques: (1) the quick screening test of trigeminal sensitivity involves patients rating the intensity of ammonium vapour presented in a lipstick-like container. (2) The lateralisation test requires subjects to identify which nasal cavity is being stimulated by a trigeminal stimulus, such as eucalyptol or menthol, while the other side receives an odourless stimulus. (3) The trigeminal sticks test evaluates the trigeminal function similarly to the olfactory function using sticks filled with trigeminal stimulant liquids. (4) The automated CO2 stimulation device is used for measuring trigeminal pain thresholds, utilising intranasal CO2 stimuli to define the pain threshold. KEY MESSAGES: Assessing intranasal trigeminal function clinically may prove useful in evaluating rhinology patients, particularly those who encounter nasal obstruction without anatomical blockage and those experiencing olfactory disorders with suspected trigeminal dysfunction. Despite their limitations, the presented methods may provide useful information about nasal patency, chemosensitivity, and pain sensation in the daily clinical practice of such patients, leading to better therapeutic decisions.

Morphology of GNAT3-immunoreactive chemosensory cells in the nasal cavity and pharynx of the rat.

Solitary chemosensory cells and chemosensory cell clusters are distributed in the pharynx and larynx. In the present study, the morphology and reflexogenic function of solitary chemosensory cells and chemosensory cell clusters in the nasal cavity and pharynx were examined using immunofluorescence for GNAT3 and electrophysiology. In the nasal cavity, GNAT3-immunoreactive solitary chemosensory cells were widely distributed in the nasal mucosa, particularly in the cranial region near the nostrils. Solitary chemosensory cells were also observed in the nasopharynx. Solitary chemosensory cells in the nasopharyngeal cavity were barrel like or slender in shape with long lateral processes within the epithelial layer to attach surrounding ciliated epithelial cells. Chemosensory cell clusters containing GNAT3-immunoreactive cells were also detected in the pharynx. GNAT3-immunoreactive cells gathered with SNAP25-immunoreactive cells in chemosensory clusters. GNAT3-immunoreactive chemosensory cells were in close contact with a few SP- or CGRP-immunoreactive nerve endings. In the pharynx, GNAT3-immunoreactive chemosensory cells were also attached to P2X3-immunoreactive nerve endings. Physiologically, the perfusion of 10 mM quinine hydrochloride (QHCl) solution induced ventilatory depression. The QHCl-induced reflex was diminished by bilateral section of the glossopharyngeal nerve, suggesting autonomic reflex were evoked by chemosensory cells in pharynx but not in nasal mucosa. The present results indicate that complex shape of nasopharyngeal solitary chemosensory cells may contribute to intercellular communication, and pharyngeal chemosensory cells may play a role in respiratory depression.

Active expiratory oscillator regulates nasofacial and oral motor activities in rats.

NEW FINDINGS: What is the central question of this study? Does the parafacial respiratory group (pFRG), which mediates active expiration, recruit nasofacial and oral motoneurons to coordinate motor activities that engage muscles controlling airways in rats during active expiration. What is the main finding and its importance? Hypercapnia/acidosis or pFRG activation evoked active expiration and stimulated the motoneurons and nerves responsible for the control of nasofacial and oral airways patency simultaneously. Bilateral pFRG inhibition abolished active expiration and the simultaneous nasofacial and oral motor activities induced by hypercapnia/acidosis. The pFRG is more than a rhythmic oscillator for expiratory pump muscles: it also coordinates nasofacial and oral motor commands that engage muscles controlling airways. ABSTRACT: Active expiration is mediated by an expiratory oscillator located in the parafacial respiratory group (pFRG). Active expiration requires more than contracting expiratory muscles as multiple cranial nerves are recruited to stabilize the naso- and oropharyngeal airways. We tested the hypothesis that activation of the pFRG recruits facial and trigeminal motoneurons to coordinate nasofacial and oral motor activities that engage muscles controlling airways in rats during active expiration. Using a combination of electrophysiological and pharmacological approaches, we identified brainstem circuits that phase-lock active expiration, nasofacial and oral motor outputs in an in situ preparation of rat. We found that either high chemical drive (hypercapnia/acidosis) or unilateral excitation (glutamate microinjection) of the pFRG evoked active expiration and stimulated motoneurons (facial and trigeminal) and motor nerves responsible for the control of nasofacial (buccal and zygomatic branches of the facial nerve) and oral (mylohyoid nerve) motor outputs simultaneously. Bilateral pharmacological inhibition (GABAergic and glycinergic receptor activation) of the pFRG abolished active expiration and the simultaneous nasofacial and oral motor activities induced by hypercapnia/acidosis. We conclude that the pFRG provides the excitatory drive to phase-lock rhythmic nasofacial and oral motor circuits during active expiration in rats. Therefore, the pFRG is more than a rhythmic oscillator for expiratory pump muscles: it also coordinates nasofacial and oral motor commands that engage muscles controlling airways in rats during active expiration.

Photoactivation of olfactory sensory neurons does not affect action potential conduction in individual trigeminal sensory axons innervating the rodent nasal cavity.

Olfactory and trigeminal chemosensory systems reside in parallel within the mammalian nose. Psychophysical studies in people indicate that these two systems interact at a perceptual level. Trigeminal sensations of pungency mask odour perception, while olfactory stimuli can influence trigeminal signal processing tasks such as odour localization. While imaging studies indicate overlap in limbic and cortical somatosensory areas activated by nasal trigeminal and olfactory stimuli, there is also potential cross-talk at the level of the olfactory epithelium, the olfactory bulb and trigeminal brainstem. Here we explored the influence of olfactory and trigeminal signaling in the nasal cavity. A forced choice water consumption paradigm was used to ascertain whether trigeminal and olfactory stimuli could influence behaviour in mice. Mice avoided water sources surrounded by both volatile TRPV1 (cyclohexanone) and TRPA1 (allyl isothiocyanate) irritants and the aversion to cyclohexanone was mitigated when combined with a pure odorant (rose fragrance, phenylethyl alcohol, PEA). To determine whether olfactory-trigeminal interactions within the nose could potentially account for this behavioural effect we recorded from single trigeminal sensory axons innervating the nasal respiratory and olfactory epithelium using an isolated in vitro preparation. To circumvent non-specific effects of chemical stimuli, optical stimulation was used to excite olfactory sensory neurons in mice expressing channel-rhodopsin (ChR2) under the olfactory marker protein (OMP) promoter. Photoactivation of olfactory sensory neurons produced no modulation of axonal action potential conduction in individual trigeminal axons. Similarly, no evidence was found for collateral branching of trigeminal axon that might serve as a conduit for cross-talk between the olfactory and respiratory epithelium and olfactory dura mater. Using direct assessment of action potential activity in trigeminal axons we observed neither paracrine nor axon reflex mediated cross-talk between olfactory and trigeminal sensory systems in the rodent nasal cavity. Our current results suggest that olfactory sensory neurons exert minimal influence on trigeminal signals within the nasal cavity.

Activation of TRPA1 by volatile organic chemicals leading to sensory irritation.

Many volatile organic chemicals (VOCs) have not been tested for sensory pulmonary irritation. Development of in vitro non-animal sensory irritation assay suitable for a large number of chemicals is needed to replace the mouse assay. An adverse outcome pathway (AOP) is designed to provide a clear description of the biochemical and cellular processes leading to toxicological effects or an adverse outcome. The AOP for chemical sensory pulmonary irritation was developed according to the Organization for Economic Co-operation and Development guidance including the Bradford Hill criteria for a weight of evidence to determine the confidence of the AOP. The proposed AOP is based on an in-depth review of the relevant scientific literature to identify the initial molecular event for respiratory irritation. The activation of TRPA1 receptor (transient receptor potential cation channel, subfamily A, member 1) is the molecular initial event (MIE) leading to sensory irritation. A direct measure of TRPA1 activation in vitro should identify chemical sensory irritants and provide an estimate of potency. Fibroblasts expressing TRPA1 are used to determine TRPA1 activation and irritant potency. We report a linear relationship between the in vivo RD50 and the in vitro pEC50 values (R=0.81) to support this hypothesis. We propose that this in vitro assay after additional analysis and validation could serve as a suitable candidate to replace the mouse sensory irritation assay.

Novel insights into the glia limitans of the olfactory nervous system.

Olfactory ensheathing cells (OECs) are often described as being present in both the peripheral and the central nervous systems (PNS and CNS). Furthermore, the olfactory nervous system glia limitans (the glial layer defining the PNS-CNS border) is considered unique as it consists of intermingling OECs and astrocytes. In contrast, the glia limitans of the rest of the nervous system consists solely of astrocytes which create a distinct barrier to Schwann cells (peripheral glia). The ability of OECs to interact with astrocytes is one reason why OECs are believed to be superior to Schwann cells for transplantation therapies to treat CNS injuries. We have used transgenic reporter mice in which glial cells express DsRed fluorescent protein to study the cellular constituents of the glia limitans. We found that the glia limitans layer of the olfactory nervous system is morphologically similar to elsewhere in the nervous system, with a similar low degree of intermingling between peripheral glia and astrocytes. We found that the astrocytic layer of the olfactory bulb is a distinct barrier to bacterial infection, suggesting that this layer constitutes the PNS-CNS immunological barrier. We also found that OECs interact with astrocytes in a similar fashion as Schwann cells in vitro. When cultured in three dimensions, however, there were subtle differences between OECs and Schwann cells in their interactions with astrocytes. We therefore suggest that glial fibrillary acidic protein-reactive astrocyte layer of the olfactory bulb constitutes the glia limitans of the olfactory nervous system and that OECs are primarily "PNS glia."

Vagus nerve stimulation modulates the cranial trigeminal autonomic reflex.

OBJECTIVE: The trigeminal autonomic reflex plays an important role in primary headache syndromes. Noninvasive vagal nerve stimulation (nVNS) may be an effective modulator of this reflex. METHODS: Twenty-two healthy volunteers underwent kinetic oscillation stimulation (KOS) of the left nostril as a reliable trigger of the trigeminal autonomic reflex. Previous to KOS, left cervical nVNS, sham simulation, or no stimulation was applied. Lacrimation was quantified using the standardized Schirmer ll test. RESULTS: Treatment with cervical nVNS significantly reduced lacrimation between no stimulation and nVNS on the ipsilateral side (minute 5: p = 0.026, ηp2 = 0.85, 95% confidence interval [CI] = 1.39-18.04; no stimulation: minute 5, 14.4 ± 9.3 mm; nVNS: minute 5, 4.7 ± 8.6 mm, mean ± standard deviation) as well as between sham stimulation and nVNS (minute 5: p = 0.030, ηp2 = 0.85, 95% CI = 1.04-17.24; sham: minute 5, 13.9 ± 6.4 mm). On the contralateral side, no significant increase between baseline and KOS was observed for nVNS (minute 5: p = 0.614, d = 0.12, 95% CI = -7.09 to 4.31; minute 5, 1.4 ± 11.5 mm) compared to both sham stimulation (minute 5: p = 0.023, d = 0.57, 95% CI = -11.46 to -0.96; minute 5, 6.2 ± 10.9 mm) and no stimulation (minute 5: p < 0.030, d = 0.62, 95% CI = -13.45 to -0.81; minute 5, 7.1 ± 11.4 mm). INTERPRETATION: Cervical nVNS resulted in a robust bilateral reduction of provoked lacrimation. This effect could be mediated either by direct bilateral activation of structures such as the nucleus of the solitary tract or by a top-down modulation via the hypothalamus. Ann Neurol 2018;84:886-892.

Endonasal anatomy of the olfactory neural network: Surgical implications.

OBJECTIVES/HYPOTHESIS: Define the anatomic distribution of the olfactory filaments within specific mucosal regions of the nasal cavity. STUDY DESIGN: Cadaveric study. METHODS: Seventeen cadaveric specimens (34 sides) were dissected to study the anatomical distribution and density of olfactory fila within different regions of the nasal cavity. Olfactory fila were dissected retrogradely to their point of entry into the anterior cranial fossa through the cribriform plate. Anatomic relationships among various components of the olfactory system and their corresponding arterial supply were determined subjectively. RESULTS: The highest density of olfactory fila was found at the mucosa of the ethmoid roof and superior turbinates. Olfactory fila were found at regions not previously considered to be part of the olfactory system: lateral wall of the nose, ethmoidal bullae, and between the os sphenoidale and arc of the posterior choana. Furthermore, at the septum, 20% of the olfactory fila crossed contralaterally before exiting the nose. The anterior ethmoidal arteries were the primary blood supply to the olfactory epithelium. CONCLUSIONS: This study suggests that olfactory filaments extend beyond previously established boundaries. These findings may have clinical implications regarding oncologic resections and could serve as the foundation for the development of techniques that better preserve olfactory function. LEVEL OF EVIDENCE: NA Laryngoscope, 2473-2477, 2018.

Myelination of the developing lateral olfactory tract and anterior commissure.

Both the lateral olfactory tract (LOT) and anterior limb of the anterior commissure (AC) carry olfactory information. The LOT forms the projection from the olfactory bulb to the ipsilateral olfactory cortices, while the AC carries odor information across the midline to the contralateral olfactory cortex and bulb. The LOT and AC differ on a number of dimensions, including early development and functional onset. The present work, examining their myelination in mice, reveals additional important differences. For example, the LOT initiates myelination 3-4 days earlier than the AC, evidenced by both an earlier increase in myelin basic protein staining seen with immunohistochemistry and an earlier appearance of myelinated fibers using electron microscopy. While both exhibit a period of rapid myelination, it occurs 4-5 days earlier in the LOT than the AC. The tracts also respond differently to early sensory restriction. Unilateral naris occlusion from the day after birth to postnatal day 30 had no consistent effects on the AC but resulted in significantly thinner myelin sheaths relative to axon caliber in the LOT. Finally, the two tracts differ structurally (the LOT contains larger, more densely packed axons with significantly thicker myelin sheaths resulting in a conduction velocity that is more than twice as fast as the AC). The findings indicate that these two large, accessible tracts provide an important means for studying brain maturation due to basic differences in both the timing of their maturation and general organization.

Neurophysiological Identification of Cranial Nerves During Endoscopic Endonasal Surgery of Skull Base Tumors: Pilot Study Technical Report.

INTRODUCTION: Intraoperative identification of cranial nerves is crucial for safe surgery of skull base tumors. Currently, only a small number of published papers describe the technique of trigger electromyography (t-EMG) in endoscopic endonasal removal of such tumors. OBJECTIVE: To assess the effectiveness of t-EMG in preventing intraoperative cranial nerve damage in endoscopic endonasal surgery of skull base tumors. MATERIALS AND METHODS: Nine patients were operated on using the endoscopic endonasal approach within a 1-year period. The tumors included large skull base chordomas and trigeminal neurinomas localized in the cavernous sinus. During the surgical process, cranial nerve identification was carried out using monopolar and bipolar t-EMG methods. Assessment of cranial nerve functional activity was conducted both before and after tumor removal. RESULTS: We mapped 17 nerves in 9 patients. Third, fifth, and sixth cranial nerves were identified intraoperatively. There were no cases of postoperative functional impairment of the mapped cranial nerves. In one case we were unable to get an intraoperative response from the fourth cranial nerve and observed its postoperative transient plegia (the function was normal before surgery). CONCLUSION: t-EMG allows surgeons to control the safety of cranial nerves both during and after skull base tumor removal.

Dose-Response Functions for the Olfactory, Nasal Trigeminal, and Ocular Trigeminal Detectability of Airborne Chemicals by Humans.

We gathered from the literature 47 odor and 37 trigeminal (nasal and ocular) chemesthetic psychometric (i.e., detectability or dose-response) functions from a group of 41 chemicals. Vapors delivered were quantified by analytical methods. All functions were very well fitted by the sigmoid (logistic) equation: y = 1 / (1 + e({-(x-C)/D})), where parameter C quantifies the detection threshold concentration and parameter D the steepness of the function. Odor and chemesthetic functions showed no concentration overlap: olfactory functions grew along the parts per billion (ppb by volume) range or lower, whereas trigeminal functions grew along the part per million (ppm by volume) range. Although, on average, odor detectability rose from chance detection to perfect detection within 2 orders of magnitude in concentration, chemesthetic detectability did it within one. For 16 compounds having at least 1 odor and 1 chemesthetic function, the average gap between the 2 functions was 4.6 orders of magnitude in concentration. A quantitative structure-activity relationship (QSAR) using 5 chemical descriptors that had previously described stand-alone odor and chemesthetic threshold values, also holds promise to describe, and eventually predict, olfactory and chemesthetic detectability functions, albeit functions from additional compounds are needed to strengthen the QSAR.

[АNTINOCICEPTIVE PROTECTION ON A STAGE OF CONCLUDING OF SURGICAL INTERVENTION AND EARLY POSTOPERATIVE PERIOD].

Efficacy of antinociceptive defense at the terminal period of operation and in early (6 h) postoperative period, using additional injection of phentanil, paracetamol and nalbufin in anesthesiological support, and applying sevofluran in 107 patients, оperated on facial skull, in 2 stage of operative risk in accordance to ASA, was a nalyzed. Insufficient antinociceptive protection at the end of operation and in early postoperative period while using phentanil and nonsteroidal antiinflammatory medicines only for anesthesia, was established, basing on analysis of hemodynamic indices, pain syndrome severity and indices of metabolic stress. Application of paracetamol have promoted raising of the antinociceptive protection efficacy during short period (up to 2 h) only. Prescription of nalbufin have had guaranteed enhanced efficacy and duration of antinociceptive protection in early postoperative period, that's why its wide application is recommended.

A new method of identifying the posterior inferior nasal nerve: implications for posterior nasal neurectomy.

INTRODUCTION: Posterior nasal neurectomy is an effective way of treating recalcitrant rhinitis. The aim of this study is to describe the anatomic relationship between the posterior inferior nasal nerve (PINN) and the structures that might be important for posterior nasal neurectomy. MATERIALS AND METHODS: An anatomic study was conducted in a university hospital dissection laboratory with 15 formalin-fixed, sagittally cut adult cadaver heads. The distance between PINN and (1) nasal sill, (2) maxillary sinus ostium, (3) posterior fontanel, (4) torus tubarius, and (5) crista ethmoidalis was measured and the location of PINN with respect to the sphenopalatine artery was assessed to define the exact location of PINN. RESULTS: The mean distance between PINN and nasal sill (56.4 mm), maxillary sinus ostium (27 mm), posterior fontanel (12.5 mm), torus tubarius (13 mm), and crista ethmoidalis (8 mm) was determined. PINN was found consistently posterior to the sphenopalatine artery where the inferior turbinate attaches to the lateral nasal wall. CONCLUSION: Instead of finding PINN around the sphenopalatine foramen, PINN can be located more easily posterior to the sphenopalatine artery where the inferior turbinate attaches to the lateral nasal wall without cauterizing the sphenopalatine artery.

The nasal cavity of the sheep and its olfactory sensory epithelium.

Macro and microdissection methods, conventional histology and immunohistochemical procedures were used to investigate the nasal cavity and turbinate complex in fetal and adult sheep, with special attention to the ethmoturbinates, the vestibular mucosa, and the septal mucosa posterior to the vomeronasal organ. The ectoturbinates, which are variable in number and size, emerge and develop later than the endoturbinates. The olfactory sensory epithelium is composed of basal cells, neurons, and sustentacular cells organized in strata, but numerous different types are distinguishable on the basis of their thickness and other properties; all variants are present on the more developed turbinates, endoturbinates II and III. Mature neurons and olfactory nerve bundles express olfactory marker protein. We found no structure with the characteristics that in mouse define the septal organ or the ganglion of Grüneberg. Our results thus suggest that in sheep olfactory sensory neurons are exclusively concentrated in the main olfactory epithelium and (to a lesser extent) in the vomeronasal organ.

The membrane proteome of sensory cilia to the depth of olfactory receptors.

In the nasal cavity, the nonmotile cilium of olfactory sensory neurons (OSNs) constitutes the chemosensory interface between the ambient environment and the brain. The unique sensory organelle facilitates odor detection for which it includes all necessary components of initial and downstream olfactory signal transduction. In addition to its function in olfaction, a more universal role in modulating different signaling pathways is implicated, for example, in neurogenesis, apoptosis, and neural regeneration. To further extend our knowledge about this multifunctional signaling organelle, it is of high importance to establish a most detailed proteome map of the ciliary membrane compartment down to the level of transmembrane receptors. We detached cilia from mouse olfactory epithelia via Ca(2+)/K(+) shock followed by the enrichment of ciliary membrane proteins at alkaline pH, and we identified a total of 4,403 proteins by gel-based and gel-free methods in conjunction with high resolution LC/MS. This study is the first to report the detection of 62 native olfactory receptor proteins and to provide evidence for their heterogeneous expression at the protein level. Quantitative data evaluation revealed four ciliary membrane-associated candidate proteins (the annexins ANXA1, ANXA2, ANXA5, and S100A5) with a suggested function in the regulation of olfactory signal transduction, and their presence in ciliary structures was confirmed by immunohistochemistry. Moreover, we corroborated the ciliary localization of the potassium-dependent Na(+)/Ca(2+) exchanger (NCKX) 4 and the plasma membrane Ca(2+)-ATPase 1 (PMCA1) involved in olfactory signal termination, and we detected for the first time NCKX2 in olfactory cilia. Through comparison with transcriptome data specific for mature, ciliated OSNs, we finally delineated the membrane ciliome of OSNs. The membrane proteome of olfactory cilia established here is the most complete today, thus allowing us to pave new avenues for the study of diverse molecular functions and signaling pathways in and out of olfactory cilia and thus to advance our understanding of the biology of sensory organelles in general.

Therapeutic effectiveness of endoscopic vidian neurectomy for the treatment of vasomotor rhinitis.

CONCLUSION: Our results indicate that vidian neurectomy may be recommended as an effective method for the treatment of vasomotor rhinitis (VMR). OBJECTIVE: The aim of this work was to study the feasibility and effectiveness of vidian neurectomy treatment under the nasal endoscope for VMR. METHODS: The study included 45 patients with VMR. They were all assigned to functional endoscopic surgery with vidian neurectomy. RESULTS: The obtained data showed that, using the rhinoconjunctivitis quality of life questionnaire, vidian neurectomy treatment relieved the symptoms of VMR in 82.2% of the patients. Vidian neurectomy also led to the reduction of expression of several cytokines, including vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, interleukin (IL)-4, and IL-5.

Endoscopic approach to the trigeminal nerve: an anatomic study.

OBJECTIVE: To describe an endoscopic perspective of the surgical anatomy of the trigeminal nerve. METHODS: Nine adult cadaveric heads were dissected endoscopically. RESULTS: Opening the pterygopalatine fossa is important because many key anatomical structures (V2, pterygopalatine ganglion, vidian nerve) can be identified and traced to other areas of the trigeminal nerve. From the pterygopalatine ganglion, the maxillary nerve and vidian nerve can be identified, and they can be traced to the gasserian ganglion and internal carotid artery. An anteromedial maxillectomy increases the angle of approach from the contralateral nares due to an increase in diameter of the piriform aperture, and provides excellent access to the mandibular nerve, the petrous carotid, and the cochlea. CONCLUSIONS: Identification of key anatomical structures in the pterygopalatine fossa can be used to identify other areas of the trigeminal nerve, and an anteromedial maxillectomy is necessary to expose the ipsilateral mandibular nerve and contralateral cranial level of the trigeminal nerve.

Olfaction: anatomy, physiology, and disease.

The olfactory system is an essential part of human physiology, with a rich evolutionary history. Although humans are less dependent on chemosensory input than are other mammals (Niimura 2009, Hum. Genomics 4:107-118), olfactory function still plays a critical role in health and behavior. The detection of hazards in the environment, generating feelings of pleasure, promoting adequate nutrition, influencing sexuality, and maintenance of mood are described roles of the olfactory system, while other novel functions are being elucidated. A growing body of evidence has implicated a role for olfaction in such diverse physiologic processes as kin recognition and mating (Jacob et al. 2002a, Nat. Genet. 30:175-179; Horth 2007, Genomics 90:159-175; Havlicek and Roberts 2009, Psychoneuroendocrinology 34:497-512), pheromone detection (Jacob et al. 200b, Horm. Behav. 42:274-283; Wyart et al. 2007, J. Neurosci. 27:1261-1265), mother-infant bonding (Doucet et al. 2009, PLoS One 4:e7579), food preferences (Mennella et al. 2001, Pediatrics 107:E88), central nervous system physiology (Welge-Lüssen 2009, B-ENT 5:129-132), and even longevity (Murphy 2009, JAMA 288:2307-2312). The olfactory system, although phylogenetically ancient, has historically received less attention than other special senses, perhaps due to challenges related to its study in humans. In this article, we review the anatomic pathways of olfaction, from peripheral nasal airflow leading to odorant detection, to epithelial recognition of these odorants and related signal transduction, and finally to central processing. Olfactory dysfunction, which can be defined as conductive, sensorineural, or central (typically related to neurodegenerative disorders), is a clinically significant problem, with a high burden on quality of life that is likely to grow in prevalence due to demographic shifts and increased environmental exposures.

Phagocytosis of bacteria by olfactory ensheathing cells and Schwann cells.

Opportunistic bacterial infections of the nasal cavity could potentially lead to infection of the brain if the olfactory or trigeminal nerves are colonised. The olfactory nerve may be a more susceptible route because primary olfactory neurons are in direct contact with the external environment. Peripheral glia are known to be able to phagocytose some species of bacteria and may therefore provide a defence mechanism against bacterial infection. As the nasal cavity is frequently exposed to bacterial infections, we hypothesised that the olfactory and trigeminal nerves within the nasal cavity could be subjected to bacterial colonisation and that the olfactory ensheathing cells and Schwann cells may be involved in responding to the bacterial invasion. We have examined the ability of mouse OECs and Schwann cells from the trigeminal nerve and dorsal root ganglia to phagocytose Escherichia coli and Burkholderia thailandensis in vitro. We found that all three sources of glia were equally able to phagocytose E. coli with 75-85% of glia having phagocytosed bacteria within 24h. We also show that human OECs phagocytosed E. coli. In contrast, the mouse OECs and Schwann cells had little capacity to phagocytose B. thailandensis. Thus subtypes of peripheral glia have similar capacities for phagocytosis of bacteria but show selective capacity for the two different species of bacteria that were examined. These results have implications for the understanding of the mechanisms of bacterial infections as well as for the use of glia for neural repair therapies.