Olfactory Nerve Fibers Research Articles

Cribriform Plate Foramina Count in Patients With Acquired and Congenital Anosmia.

Cribriform foramina provide the openings for olfactory nerve fibers to cross from the nasal cavity to the olfactory bulb. Disruption of the olfactory nerve fibers is known to affect olfactory function, but little is known about the potential effects on the number of cribriform foramina in congenital anosmia. This pilot study aimed to investigate whether there was a reduction in foramina in patients with acquired and congenital anosmia (including both Kallmann syndrome and isolated congenital anosmia) compared to controls with normal olfactory function. Paranasal CT image stacks were analyzed from 20 patients with congenital anosmia (n = 6), acquired anosmia (n = 6), or normal olfactory function (n = 8). Cribriform foramina were counted by three observers from the slice revealing the crista galli and the ethmoidal slits. The two closest values for each subject were analyzed in comparison across the three groups using one-way analysis of variance. Patients with congenital, but not acquired, anosmia had significantly fewer cribriform foramina (x̄ ± SE = 10.17 ± 1.23) compared to healthy, normosmic controls (x̄ ± SE = 19.88 ± 2.01). There was no significant difference in foramina count between congenital and acquired anosmics (x̄ ± SE = 15.83 ± 3.47). In this pilot study, a reduced number of cribriform foramina was found in individuals with congenital anosmia. Examination of cribriform foramina could be helpful in counseling patients with olfactory loss. Further investigation in larger studies with additional cohorts is warranted.

Pneumolysin contributes to dysfunction of nasal epithelial barrier for promotion of pneumococcal dissemination into brain tissue.

Streptococcus pneumoniae is one of the major pathogens responsible for bacterial meningitis and neurological sequelae. The present study was conducted to identify a non-hematogenous route used by S. pneumoniae to gain access to brain tissue without causing bacteremia or pneumonia, as well as bacterial and host factors involved in this process. To investigate the molecular mechanisms and dissemination pathways of pneumococcal infection in brain tissue, mice were intranasally inoculated with S. pneumoniae strain EF3030, a clinical isolate from a patient with otitis media. Pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum, with neither bacteremia nor pneumonia observed in the present model. Immunostaining imaging revealed the presence of S. pneumoniae organisms in olfactory nerve fibers. Knockout of the ply gene encoding pneumolysin (PLY) markedly compromised the ability of the bacterial organisms to disseminate into brain tissue, whereas the dissemination efficiency of the complemented strain was restored to nearly the same level as the wild type. Notably, distinct upregulation of Gli1 and Snail1, which are involved in the transcriptional repression of junctional proteins, along with downregulation of E-cadherin, was detected in nasal lavage samples from mice infected with the wild-type or complemented strain, but not in those from mice infected with the ply mutant. Taken together, the present findings indicate that PLY induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, thus allowing pneumococcal dissemination to brain tissue that occurs in a non-hematogenous manner.IMPORTANCEBacterial meningitis, considered to be caused by bacteremia, can lead to blood-brain barrier disruption and bacterial dissemination into the central nervous system. Despite the availability of intravenously administered antibiotics with cerebrospinal fluid transferability, bacterial meningitis remains associated with high rates of morbidity and mortality. Here, we utilized Streptococcus pneumoniae strain EF3030, clinically isolated from otitis media, for the construction of a murine infection model to investigate the molecular mechanisms by which nasally colonized pneumococci disseminate into brain tissue. The obtained findings indicate that pneumolysin (PLY) induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, which facilitates pneumococcal dissemination to brain tissue in a non-hematogenous manner. Our results support the existence of an alternative route by which S. pneumoniae can reach the central nervous system and indicate the need for the development of novel therapeutic strategies, which would be an important contribution to the clinical management of bacterial meningitis.

Histological changes in the olfactory bulb and rostral migratory stream due to interruption of olfactory input

ObjectivePeriglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone, migrate to the olfactory bulb via the Rostral Migratory Stream (RMS), and differentiate into mature cells within the olfactory bulb throughout postnatal life. While the regulation of neuroblast development is known to be affected by external stimuli, there is a lack of information concerning changes that occur during the recovery process after injury caused by external stimuli. To address this gap in research, the present study conducted histological observations to investigate changes in the olfactory bulb and RMS occurring after the degeneration and regeneration of olfactory neurons. MethodsTo create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test. ResultsOlfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days. ConclusionThese results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input.

Infiltration of peripheral immune cells into the olfactory bulb in a mouse model of acute nasal inflammation

Chronic nasal inflammation induces robust olfactory bulb (OB) atrophy in mice. Here we examined initial events that occur in the OB after bilateral intranasal administration of lipopolysaccharide, focusing on the olfactory nerve fibers and meninges. We analyzed the time course of OB and meninges inflammation using histological and biochemical approaches. Within 12 h, we observed increased chemokine expression and transient infiltration of peripheral immune cells into the OB, resulting in the development of pro-inflammatory status in the OB. Meningeal immunity was activated. Resident microglia produced anti-inflammatory cytokines within 24 h. These could be the initial events that lead to OB atrophy.

High-dose IgG suppresses local inflammation and facilitates functional recovery after olfactory system injury.

ObjectiveHead trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti‐inflammatory treatment using steroids or anti‐cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high‐dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury.MethodsOlfactory nerve transection (NTx) was performed in OMP‐tau‐lacZ mice to establish injury models. High‐dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X‐gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test.ResultsHigh‐dose IgG‐injected mice showed significantly smaller areas of injury‐associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG‐injected mice.InterpretationThese findings suggest that high‐dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

A Transmission Electron Microscopic Study of the Olfactory Epithelium in Hill Stream Cyprinidiae, Garra mullya (Sykes)

Olfaction is primarily produced by the stimulation of receptor cells on the olfactory organ's neuroepithelial surface, surrounded by olfactory nerve fibres. Numerous fish life processes, including migration, communication, feeding, schooling, defence, and reproduction, depend heavily on olfactory signals and cues. The olfactory and reproductory systems are interconnected structurally and functionally, and puberty-related alterations in the olfactory epithelium are documented. The olfactory epithelium, which covers a large portion of the surface of the olfactory rosette, a structure found within the olfactory chambers on the fish rostrum, is where the olfactory receptor cells are situated. Although ultra structural transmission electron microscopic studies of the olfactory organ and bulb are carried out by some investigators but very sparse information is available on hillstream fishes and that is why this work has been undertaken to detail the structure of olfactory system in G. mullya by electron microscopy. Microvillous olfactory receptor cells are placed compactly adjacent to the supporting cell showing a junction complex : the zonula-ocludens. Polygonal white cells are present in between the basal cells and supporting cells. Small polyhedral basal cells lie just above the basal lamina of olfactory epithelium. Basal cells may be working as stem cells for regeneration of lost or damaged non sensory and goblet cells.

Mechanism of olfactory deficit in neurotrauma and its related affective distress: A narrative review.

Traumatic brain injury (TBI) is among the leading causes of death and disability all over the globe. TBI is also commonly associated with clinical sequelae of posttraumatic depression, and reports of other subsequent affective distress are common. Similarly, posttraumatic changes in chemoreceptive sensory functions, primarily due to coup-contrecoup injury induced shearing of the olfactory nerve fibers, leading to anosmia and ageusia are also well documented in the literature. However, the current literature is limited in addressing the intersections between said variables. The aim of this study was to provide a focused narrative review of the literature, to address these intersections found in clinical sequelae of TBI. As chemoreceptive sensory deficits are also linked to significant affective distress of their own, this review addresses the bidirectionality between sensory deficit and affective distress. Prevalence, demographics, mechanisms, and clinical implications are presented. Previous research is presented and discussed, in an effort to highlight the importance of consideration for all factors in TBI patient care and future research.

HPV-Related Multi-Phenotypic Sinonasal Carcinoma with Aggressive Clinical Behavior; A Rare Case

Abstract Introduction/Objective Human Papilloma Virus (HPV)-related multiphenotypic sinonasal carcinoma, previously known as HPV-related sinonasal carcinoma with adenoid cystic carcinoma-like features, is a rare type of sinonasal carcinoma with both epithelial-derived and salivary gland-type morphologic features. It is associated with high-risk HPV, but lacks MYB gene rearrangements. Methods/Case Report We report a case of a 59-year-old male who presented with a rapidly growing sinonasal mass. On MRI, a left nasal cavity lesion was identified growing laterally along the frontal process of the maxilla, extending into the middle meatus and into the maxillary sinus. Patient underwent a complex left medial maxillectomy, spheno- ethmoidectomy, and sinusotomy. On gross evaluation, the left inferior turbinate and sidewall demonstrated a 4 cm unremarkable turbinate with attached friable soft tissue. Microscopic examination revealed sections of carcinoma with various architectural patterns comprised of foci with adenoid cystic carcinoma-like morphology, basaloid squamous cell carcinoma and adenocarcinoma. The tumor showed positive immunostaining for P40, but focal reactivity to S100 and rare scattered reactivity with CD117. INI-1 immunostain was retained in tumor cells. P16 immunostain was strong and diffuse and high-risk cocktail HPV RNA ISH was positive. However, MYB FISH testing was equivocal. Morphologic and immunophenotypic findings were consistent with HPV-related multiphenotypic sinonasal carcinoma. The tumor involved the olfactory nerve fibers requiring a skull base resection and showed extension into the dura mater. Results (if a Case Study enter NA) NA Conclusion HPV related multiphenotypic sinonasal carcinoma is a recently described entity that can pose significant diagnostic challenge. It typically has an indolent clinical course with potential for late recurrences. This case study highlights the potential aggressive nature of this type of sinonasal carcinoma, despite association with high-risk HPV, and use of ancillary testing in aiding diagnosis.

Enigmatic Neural Pathways: Potentiating Viral Neuroinvasion Into the CNS.

Enigmatic Neural Pathways: Potentiating Viral Neuroinvasion Into the CNS.

COVID-19 related olfactory impairment – diagnostics, significance and treatment

Aim: Smell disorders are frequent symptoms of COVID-19 disease. This systematic review covers the pathophysiology, diagnostics, prognostic significance, and treatment of COVID-19 related smell disorders. Methods: The articles were selected in accordance with the PRISMA guidelines. The inclusion criteria were: 1. peer-reviewed publications;2. studies on human subjects;3. studies published in English or Czech;and 4. used filters: meta-analysis/systematic review/randomized controlled trial. The exclusion criteria were: 1. abstracts from conferences;2. commentaries;and 3. inclusion of subjects younger than 18 years. The databases PubMed and Web of Science were searched. Using the search term “anosmia OR smell loss OR smell disorders OR dysosmia OR parosmia AND COVID-19”, 157 papers were selected for analysis, with 109 being ruled out based on the exclusion criteria. The full texts and their references were obtained and studied, and the references meeting the inclusion criteria were also included in this review, leading to a total of 68 papers selected for the review. Results: Approximately 60% of patients with COVID-19 disease present with smell disorders. Most studies agree anosmia appears more frequently in the mild course of the disease. The inflammation and demyelination of the olfactory nerve fibres probably play a key role in the pathogenesis. Damage to the supporting cells of the olfactory epithelium may also play an important role. Olfactory disorder may persist over a varying period of time after the resolution of the acute phase of COVID-19. Olfactory training seems to be beneficial in the treatment. The data regarding the efficacy of topical corticosteroids are inconsistent. No other drugs have yet demonstrated a clinical effect. Conclusion: Loss of smell is a common accompanying symptom in mostly mild forms of COVID-19. Olfactory training seems to be effective in treating this dysfunction. Pharmacotherapy (including local and systemic corticosteroids) has not yet proven effective.

Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas.

Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas.

Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism

PurposeIdiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. MethodsWe screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. ResultsWe identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. ConclusionSEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.

Superior turbinate management and olfactory outcome after endoscopic endonasal transsphenoidal surgery for pituitary adenoma: a propensity score-matched cohort study.

BackgroundSurgical management of the superior turbinate (ST) is required to access the sella in endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenoma. Two common ST management techniques include partial resection of the ST (PRST) and intentional lateralization of the ST (ILST). Given the concentrated distribution of the olfactory nerve fibers on the medial surface of the ST, in this study we aimed to ascertain whether PRST worsens the objective olfactory outcome when compared with ILST.MethodsA retrospective, propensity score‒matched cohort study was performed at a tertiary referral center. A total of 232 adult patients undergoing EETS for pituitary adenoma were analyzed. The threshold test (STT) and the 12‐item identification test (SIT‐12) from “Sniffin’ Sticks” were administered for separate nostrils preoperatively and 6 months postoperatively.ResultsOf 232 patients, 109 had right‐sided PRST and 123 received right‐sided ILST. Propensity score matching—controlling for olfactory‐related confounding factors, including gender, age, medical comorbidities, surgical technique, and preoperative olfaction—resulted in 74 matched pairs. When comparing the 6‐month postoperative olfactory performance of the right nostril, the STT score was significantly lower in the PRST group than the ILST group (p = 0.036, η2 for effect size estimate = 0.030), but the SIT‐12 scores were similar in the 2 groups (p = 0.325). Overall, the olfactory outcomes for the right nostril did not qualitatively differ between the PRST and ILST groups (p = 0.401).ConclusionDespite its association with threshold impairment, PRST in EETS does not seem to carry an additional risk of postoperative olfactory dysfunction.

Telencephalon Cytoarchitecture of tsinling dwarf skinks (Scincella tsinlingensis)

The telencephalon of adult Scincella tsinlingensis was detected by light and electron microscopy, which will be used as the basis for further neurobiological comparative studies. The telencephalon of S. tsinlingensis was consisted of paired olfactory bulbs, paired cerebral hemispheres, and a telencephalon medium or impar. Main-olfactory bulb can be classified into six layers such as olfactory nerve fibers layer, glomerular layer, external plexiform layer, mitral layer, internal plexiform layer, granular layer and ependyma layer. The dorsal part of telencephalon contained the cortex and dorsal ventricular ridge. The cerebral cortex of S. tsinlingens was relatively thin, while the dorsal cortex was the thinnest, but gradually thickened as it extended to the medial and lateral cortex. The neural cells, glial cells and ependymal cells widely distributed in the cerebral cortex represented similar ultrastructural characteristics to those described in other vertebrates. Golgi staining revealed multipolar cell, bitufted cell and monotufted cell in three cortical layers of medial cortex. The results indicated that the cytoarchitectonic characteristics of telencephalon in S. tsinlingensis resembled those found in other lizards.

Long‐term olfaction outcomes in transnasal endoscopic skull‐base surgery: a prospective cohort study comparing electrocautery and cold knife upper septal limb incision techniques

Olfactory nerve fibers are at risk of injury during transnasal endoscopic skull-base approaches. Olfactory outcomes for various techniques have not been thoroughly investigated. This study aims to report long-term olfactory outcomes when a cold knife upper septal limb incision technique is used compared to monopolar cautery. A prospective cohort study was performed at a tertiary referral center. Adult patients undergoing endoscopic approaches with septal incisions were randomized to cold knife or monopolar cautery groups. Patient demographics, clinical history, surgical data, and outcomes were collected. Preoperative, 3-month, and 12-month postoperative scores on the University of Pennsylvania Smell Inventory Test (UPSIT) and 22-item Sino-Nasal Outcome Test (SNOT-22) were measured. Fisher's exact tests were performed for categorical variables and t tests were performed for continuous variables. Twenty-two (22) patients (10 cold knife, 12 cautery) were enrolled between March 2016 and August 2017. The average age ± standard deviation was 50.2 ± 14.0 years (p = 0.59), 54% (p = 0.69) were female, and the primary pathology was pituitary adenoma (73%, p = 1.00). Preoperative, 3-month, and 12-month postoperative UPSIT scores were similar between the cold knife and cautery groups (32.8 vs 32.4, p = 0.80; 33.1 vs 33.0, p = 0.96; 33.6 vs 33.3, p = 0.84). On the "sense of smell/taste" question of the SNOT-22, there was also no difference at all time points (p > 0.22). There was no significant change in patient UPSIT scores 1 year after transnasal skull-base approaches, and no short-term or long-term differences between cold knife and cautery upper septal limb incision techniques. Our study supports an individualized approach based on surgeon preference.

Neurodegeneration in the olfactory bulb and olfactory deficits in the Ccdc66 -/- mouse model for retinal degeneration

The Ccdc66-deficient (Ccdc66 -/-) mouse model exhibits slow progressive retinal degeneration. It is unclear whether CCDC66 protein also plays a role in the wildtype (WT; Ccdc66 +/+) mouse brain and whether the lack of Ccdc66 gene expression in the Ccdc66 -/- mouse brain may result in morphological and behavioral alterations.CCDC66 protein expression in different brain regions of the adult WT mouse and in whole brain during postnatal development was quantified by SDS-PAGE and Western blot. Ccdc66 reporter gene expression was visualized by X-gal staining. Selected brain regions were further analyzed by light and electron microscopy. In order to correlate anatomical with behavioral data, an olfactory habituation/dishabituation test was performed.CCDC66 protein was expressed throughout the early postnatal development in the WT mouse brain. In adult mice, the main olfactory bulb exhibited high CCDC66 protein levels comparable to the expression in the retina. Additionally, the Ccdc66 -/- mouse brain showed robust Ccdc66 reporter gene expression especially in adult olfactory bulb glomeruli, the olfactory nerve layer and the olfactory epithelium. Degeneration was detected in the Ccdc66 -/- olfactory bulb glomeruli at advanced age. This degeneration was also reflected in behavioral alterations; compared to the WT, Ccdc66 -/- mice spent significantly less time sniffing at the initial presentation of unknown, neutral odors and barely responded to social odors.Ccdc66 -/- mice develop substantial olfactory nerve fiber degeneration and alteration of olfaction-related behavior at advanced age. Thus, the Ccdc66 -/- mouse model for retinal degeneration adds the possibility to study mechanisms of central nervous system degeneration.

Evidence for intranasal oxytocin delivery to the brain: recent advances and future perspectives.

The neuropeptide oxytocin plays an evolutionarily conserved role in mammalian social behavior. Despite striking effects on animal social behavior after intracerebroventricular drug delivery, this delivery mode is impractical in humans. Intranasal oxytocin delivery provides a noninvasive alternative to increase central oxytocin activity, and has shown promise as a treatment for psychiatric illnesses. Intranasal oxytocin delivery is purported to increase central oxytocin concentrations via channels surrounding trigeminal and olfactory nerve fibers, which may facilitate increased activity at central oxytocin receptors. This report outlines the evidence for intranasal oxytocin delivery increasing central concentrations or activity, identifies current knowledge gaps and highlights future research opportunities. Recent efforts to enhance intranasal oxytocin delivery via improved intranasal delivery technology and dose-ranging studies are discussed.

The histological structure and histochemistry of the mucosa of the nasal conchae in geese, Anser anser

We investigated the histological structure and histochemistry of the nasal conchae of geese and compared these structures with those of other avian species. The rostral, middle and caudal conchae were dissected from the nasal cavity of eight geese, fixed in Carnoy’s solution and embedded in paraffin. The entrance of the rostral concha was lined by keratinized stratified squamous epithelium, which toward the middle concha was replaced by modified keratinized squamous epithelium, the deep layer of which opened into tubular glandular structures containing secretory epithelium on crypt-like invaginations. The lamina propria of the rostral concha contained numerous Grandry’s and Herbst corpuscles, which are pressure-sensitive receptors peculiar to waterfowl. The lamina propria of the middle concha contained solitary lymphoid follicles and lymphocyte infiltrations. The cartilaginous component of the middle concha was highly convoluted and resembled a spiral of two and a half scrolls, which were lined by pseudostratified columnar epithelium. We observed that unlike mammals, this epithelium contained mostly intraepithelial alveolar glands rather than goblet cells. The caudal concha was similar to the middle concha, but less convoluted. It was lined by olfactory epithelium and its lamina propria contained serous Bowman’s glands as well as olfactory nerve fibers. Histochemical examination demonstrated that while none of the conchae contained sulfated mucins, except for the cartilage, the intraepithelial glands of the rostral and middle conchae contained mostly carboxylated acidic mucin and some neutral mucin, and were thus of the mixed type. The outermost scroll of the spiral of the middle concha contained some periodate-Schiff stained mucins. Of the glands of the mucosa of the middle concha, the deep tubuloalveolar glands in the convex parts of the scrolls contained primarily acidic mucins, while the shallow intraepithelial alveolar glands in the concave parts of the scrolls contained primarily neutral mucins. Our findings indicate that the rostral and caudal conchae primarily have a sensory function and the middle concha participates in mucosal defense.

Anti-high mobility group box 1 antibody suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury

BackgroundRefractory olfactory dysfunction is a common finding in head trauma due to olfactory nerve injury. Anti-inflammatory treatment using steroids is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that steroids can induce side effects. The present study examines if the inhibition of proinflammatory cytokine, high mobility group box 1 (HMGB1), can facilitate olfactory functional recovery following injury.MethodsOlfactory nerve transection (NTx) was performed in OMP-tau-lacZ mice to establish injury models. We measured HMGB1 gene expression in the olfactory bulb using semi-quantitative polymerase chain reaction (PCR) assays and examined HMGB1 protein localization in the olfactory bulb using immunohistochemical staining. Anti-HMGB1 antibody was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X-gal staining labeled OMP in the degenerating and regenerating olfactory nerve fibers, and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using both an olfactory avoidance behavioral test and evoked potential recording.ResultsHMGB1 gene and protein were significantly expressed in the olfactory bulb 12 h after NTx. Anti-HMGB1 antibody-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia and an increase in regenerating nerve fibers. Both an olfactory avoidance behavioral test and evoked potential recordings showed improved functional recovery in the anti-HMGB1 antibody-injected mice.ConclusionsThese findings suggest that inhibition of HMGB1 could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

Glycoconjugate expression in the olfactory bulb of the premetamorphic larva of the Japanese sword-tailed newt (Cynops ensicauda).

We examined the organization of the olfactory organ and assessed the lectin histochemistry to investigate the glycoconjugate distribution of the olfactory bulb in premetamorphic larvae of Cynops ensicauda. The nasal cavity was an oval chamber that contained olfactory epithelium and a primitive vomeronasal organ. Secretory products were found in the supporting cells of the two sensory epithelia and in the respiratory cells. Ten lectins bound to the olfactory and vomeronasal nerve fibers as well as to the glomeruli in the olfactory bulb. The binding intensity in larvae was weaker than that reported previously in mature animals. This difference suggests a functional correlation between the expression change of glycoconjugates and the developmental refinement of the olfactory system during metamorphosis.