Recovery of taste organs and sensory function after severe loss from Hedgehog/Smoothened inhibition with cancer drug sonidegib.

Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation. Effects were selective, sparing nontaste papillae. To confirm that taste-organ effects of sonidegib treatment result from HH/SMO signaling inhibition, we studied mice with conditional global or epithelium-specific Smo deletions and observed similar effects. During sonidegib treatment, chorda tympani nerve responses to lingual chemical stimulation were maintained at 10 d but were eliminated after 16 d, associated with nearly complete TB loss. Notably, responses to tactile or cold stimulus modalities were retained. Further, innervation, which was maintained in the papilla core throughout treatment, was not sufficient to sustain TB during HH/SMO inhibition. Importantly, treatment cessation led to rapid and complete restoration of taste responses within 14 d associated with morphologic recovery in about 55% of TB. However, although taste nerve responses were sustained, TB were not restored in all fungiform papillae even with prolonged recovery for several months. This study establishes a physiologic, selective requirement for HH/SMO signaling in taste homeostasis that includes potential for sensory restoration and can explain the temporal recovery after taste dysgeusia in patients treated with HH/SMO inhibitors.

Bilateral taste disorders in patients with Ramsay Hunt syndrome and Bell palsy.

OBJECTIVE: Ramsay Hunt syndrome (RHS) and Bell palsy (BP) are typically known as facial nerve motor syndromes and are primarily unilateral. The aim of this study was to challenge this assertion, because both conditions are also known to be associated with viruses that typically affect several nerves. METHODS: Ten participants with RHS, 12 with BP, all clinically unilateral, and 12 healthy controls were prospectively enrolled. Electrogustometric thresholds were measured bilaterally in the areas of the chorda tympani, the glossopharyngeal, and the major petrosal nerve. Also bilaterally, the taste function was tested using chemogustometry with different tastant concentrations. Again bilaterally, the morphology of the mucosa and the vessels of the anterior fungiform papillae were examined by contact endoscopy. Statistically, RHS and BP participants were compared with the healthy controls, and the paretic sides of RHS and BP were compared pairwise with their mobile sides. RESULTS: Electrogustometrically, perception was reduced bilaterally in RHS (10-19dB, p < 0.001) and BP (3-5dB, p = 0.011-0.030) in all 3 innervation areas. Chemogustometrically, it was also reduced bilaterally in RHS (20-70%) and BP (8-50%). Papillary atrophies were increased 100% in RHS (p = 0.001) and BP (p < 0.001). They were more increased on the paretic side in RHS (30%, p = 0.078) and BP (83%, p < 0.001). INTERPRETATION: In these 2 clinically unilateral conditions, the gustatory perception and morphology are bilaterally affected, more in RHS and more on the paretic side. BP, known as an isolated motor condition, appears to be a cranial polyneuritis. A bilateral examination and therapeutic gustatory monitoring might follow these observations in evidence-based practice. Ann Neurol 2018;83:807-815.

Proton Pump Inhibitor Ameliorates Taste Disturbance among Patients with Laryngopharyngeal Reflux: A Randomized Controlled Study.

Patients with laryngopharyngeal reflux (LPR) were reported to suffer from hypogeusia that affects quality of life. Proton pump inhibitor (PPI) is a useful drug in the treatment of LPR, but its effect on hypogeusia is not known. We therefore assessed the effects of PPI or a histamine H2 receptor antagonist (H2 blocker) on hypogeusia among patients with LPR. Both PPI and H2 blocker could inhibit acid reflux. LPR was diagnosed with reflux finding score and reflux symptom index. The visual analogue scale (VAS) of taste disturbance symptoms and the gustatory tests were assessed before and 8 weeks after treatment with esomeprazole, a PPI (20 patients, aged 50.0 ± 1.7 years) or famotidine, a H2 blocker (20 patients, aged 47.1 ± 1.8 years). There were no significant differences in VAS scores and recognition thresholds for four basic tastes between the two groups before treatment. Only PPI therapy significantly decreased the VAS scores, suggesting the improvement of taste perception. Moreover, PPI therapy significantly decreased recognition thresholds for bitter taste in the anterior tongue (chorda tympani nerve area) and the thresholds in the posterior tongue (glossopharyngeal nerve area) for salty, sour, and bitter tastes. By contrast, H2-blocker therapy caused no significant changes of thresholds in the anterior tongue, but improved the threshold only for bitter in the posterior tongue, the value of which was however significantly higher than that in PPI group. In conclusion, PPI could ameliorate hypogeusia by improving bitter, salty, and sour tastes among patients with LPR.

Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes.NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal chemosensory neurons. We found that FAE substantially reduced taste and trigeminal responsiveness to ethanol and its flavor components.

Gustatory function in chronic otitis media (mucosal type) before and after tympanoplasty.

Chronic inflammation in the middle ear may result in functional impairment of the chorda tympani nerve, which carries taste from the anterior two-thirds of the tongue. This may lead to impaired taste sensation. Timely intervention and adequate disease clearance may help the chorda tympani nerve to recover. Gustatory function of 107 patients who underwent Tympanoplasty for Chronic otitis media (mucosal type) was evaluated in a cohort of Indian patients. To compare the preoperative and postoperative gustatory function in these patients taste scores were documented preoperatively, and at 6 weeks and 3 months postoperatively, in an effort to document taste function improvement after disease clearance. The taste scores thus obtained were recorded and analyzed. A significant improvement in taste threshold postoperatively in comparison to the preoperative taste scores (p = 0.001) was found. It was observed that age of the patient and duration of illness have a significant impact on the recovery of taste function. Our study suggests that taste perception improves over a period of time after successful tympanoplasty in patients with chronic otitis media (mucosal type).

Electrogustometry thresholds, tongue tip vascularization, and density and morphology of the fungiform papillae in diabetes.

OBJECTIVES: The aim of this study was to investigate, in parallel, changes in electrogustometric (EGM) thresholds, the morphology and density of the fungiform papillae (fPap), and the shape and density of the vessels at the tip of the human tongue in patients with diabetes mellitus (DM). METHODOLOGY: In 36 patients (19 females, 17 males; 12 subjects with type 1 DM and 24 subjects with type 2 DM), we recorded bilateral EGM-thresholds at the areas innervated by the chorda tympani, the glossopharyngeal nerves, and the greater petrosal nerves. We examined the morphology and density of the fPap and blood vessel density and morphology at the tip of the tongue with contact endoscopy (CE). A group of 36 healthy, age-matched, non-smoking individuals served as controls. RESULTS: The fPap density measured by CE was significantly (p < 0.05) reduced in DM compared to control groups. EGM-thresholds were significantly higher in the DM group than in the control group (p < 0.05). Gender did not have a significant impact on CE and EGM findings within the DM group. Body mass index did not significantly affect EGM-thresholds or the morphology and vascularization of fPap. CONCLUSION: These results suggested that DM significantly reduced gustatory function, based on EGM, and impaired the gustatory anatomical structures, based on CE. Both EGM and CE may be useful in clinical settings to monitor taste disorders in patients with DM.

Morphology of human fungiform papillae after severing chorda tympani nerve.

OBJECTIVES: We aimed to clarify the postoperative morphology of the fungiform papillae (FP) of the tongue in patients who recovered gustatory function after the chorda tympani nerve was severed during middle ear surgery. METHODS: Fifty-four patients with normal preoperative gustatory function measured by electrogustometry (EGM) were included. The proximal and distal stumps of the severed nerves were re-adapted or re-approximated during surgery to promote regeneration of the nerve. The EGM thresholds over 2 years after surgery were compared with preoperative values. At the same time, the morphological characteristics of the FP in the midlateral region of the tongue were recorded with a digital microscope. RESULTS: One month after surgery, EGM showed no response in any patients. At a time point of more than 2 years, the FP showed complete atrophy and no response to EGM on the surgical side in 21 of the 54 patients. In 16 patients who showed complete recovery of the EGM threshold (below 20 microA), the FP showed an almost normal appearance, and the mean number of FP was 77.5% (10 +/- 4.1 papillae per square centimeter) of that on the contralateral side (12.9 +/- 4.9 papillae per square centimeter; p > 0.05). CONCLUSIONS: The morphology of the FP was maintained in patients who recovered gustatory function after the chorda tympani nerve was severed. Because the results indicate regeneration of the taste buds, further observation is needed to detect regenerated taste buds in the FP.

Light and electron microscopic observation of regenerated fungiform taste buds in patients with recovered taste function after severing chorda tympani nerve.

OBJECTIVES: The aim of this study was to evaluate the mean number of regenerated fungiform taste buds per papilla and perform light and electron microscopic observation of taste buds in patients with recovered taste function after severing the chorda tympani nerve during middle ear surgery. METHODS: We performed a biopsy on the fungiform papillae (FP) in the midlateral region of the dorsal surface of the tongue from 5 control volunteers (33 total FP) and from 7 and 5 patients with and without taste recovery (34 and 29 FP, respectively) 3 years 6 months to 18 years after surgery. The specimens were observed by light and transmission electron microscopy. The taste function was evaluated by electrogustometry. RESULTS: The mean number of taste buds in the FP of patients with completely recovered taste function was significantly smaller (1.9 +/- 1.4 per papilla; p < 0.01) than that of the control subjects (3.8 +/- 2.2 per papilla). By transmission electron microscopy, 4 distinct types of cell (type I, II, III, and basal cells) were identified in the regenerated taste buds. Nerve fibers and nerve terminals were also found in the taste buds. CONCLUSIONS: It was clarified that taste buds containing taste cells and nerve endings do regenerate in the FP of patients with recovered taste function.

[Evaluation of loss of the chorda tympani function after myringoplasty]. / Miringoplasti sonrasi korda timpani fonksiyon kaybinin degerlendirilmesi.

OBJECTIVES: Loss of taste function was studied pre- and postoperatively in patients who underwent myringoplasty. PATIENTS AND METHODS: Thirty-two patients who were diagnosed with chronic otitis media and underwent myringoplasty between May 2007 and May 2009 were included in the study. Regional taste test was performed preoperatively and two weeks after the operation in all patients planned to undergo myringoplasty. For patients describing disturbance in the postoperative taste test or in the questionnaire form, the taste test was repeated at six months after the operation and the questionnaire form was completed. RESULTS: Chorda tympani was preserved in 18 patients (56.2%), traumatized in nine patients (28.1%), and cut completely in five patients (15.7%). Totally in 10 out of 32 patients (31.2%), an disturbance in the taste test was found at two weeks postoperatively. Sweetness/saltiness, bitterness, and sourness taste disturbances were found in 10, nine, and two patients, respectively. Improvements were identified in two out of 10 patients in the taste test performed at six months. The disturbances in the taste tests of eight patients continued to exist at that time. Sweetness/saltiness, bitterness, and sourness taste disturbances were found in eight, seven and two patients, respectively. CONCLUSION: The chorda tympani nerve may be traumatized or completely cut as a complication of ear surgery. Sacrificing the nerve, where it is highly traumatized by surgical devices, reduces the duration of postoperative complaints.

Earlier recovery of lingual dysfunction after middle ear surgery in pediatric versus adult patients.

OBJECTIVES: It is generally thought that the recovery of damaged chorda tympani nerve (CTN) function after middle ear surgery is different in pediatric patients from that in adult patients. The purpose of this study was to investigate the changes and the progress of taste and somatosensory functions of the tongue after middle ear surgery in pediatric patients compared with those of adult patients. STUDY DESIGN: Prospective study. METHODS: Fifty-nine pediatric patients and 106 adult patients underwent middle ear surgery. Taste and somatosensory functions of the anterior tongue, the so-called CTN functions, were assessed using electrogustometry (EGM), a 2-point discriminator, an electrostimulator, and a questionnaire before and 2 weeks and 6 months after surgery. RESULTS: Two weeks after surgery, there was no significant difference in the incidence of dysgeusia and abnormal EGM thresholds between the patient groups. The incidence of tongue numbness was significantly lower in pediatric patients than in adult patients regardless of CTN manipulation. Although the lingual somatosensory thresholds of adult patients were significantly increased, those of pediatric patients were not increased. Six months after surgery, the incidences of dysgeusia and an abnormal EGM threshold were lower in pediatric patients than in adult patients. Tongue numbness disappeared, and the thresholds of lingual somatosensory tests returned to normal in most pediatric patients. CONCLUSION: Not only taste function but also lingual somatosensory function was damaged after middle ear surgery even in pediatric patients. Pediatric patients complained of tongue numbness less frequently and showed earlier recovery than adult patients. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:1016-1022, 2020.

Behavioral and neurophysiological taste responses to sweet and salt are diminished in a model of subclinical intestinal inflammation.

There is strong evidence for gut-taste bud interactions that influence taste function, behavior and feeding. However, the effect of gut inflammation on this axis is unknown despite reports of taste changes in gastrointestinal (GI) inflammatory conditions. Lipopolysaccharide (LPS), an inflammatory stimulus derived from gram-negative bacteria, is present in the normal GI tract and levels increase during high-fat feeding and gut infection and inflammation. Recordings from the chorda tympani nerve (CT), which transmits taste information from taste buds on the anterior tongue to the brain, previously revealed a transient decrease in sucrose responses in mice that ingest LPS during a single overnight period. Here we test the effect of acute or chronic, weekly LPS gavage on licking behavior and CT responses. Using brief-access testing, rats treated with acute LPS and mice receiving acute or chronic LPS decreased licking responses to sucrose and saccharin and to NaCl in mice. In long-term (23 h) tests chronic LPS also reduced licking responses to saccharin, sucrose, and NaCl in mice. Neurophysiological recordings from the CT supported behavioral changes, demonstrating reduced responses to sucrose, saccharin, acesulfame potassium, glucose and NaCl in acute and chronic LPS groups compared to controls. Chronic LPS significantly elevated neutrophils in the small intestine and colon, but LPS was not detected in serum and mice did not display sickness behavior or lose weight. These results indicate that sweet and salt taste sensitivity could be reduced even in asymptomatic or mild localized gut inflammatory conditions such as inflammatory bowel disease.

Chorda tympani in chronic inflammatory middle ear disease.

OBJECTIVES: To study the effect of chronic inflammatory middle ear disease on gustatory function of chorda tympani nerve. METHODS: A prospective study was performed on 85 patients having unilateral chronic inflammatory middle ear disease of either cholesteatomatous or noncholesteatomatous type. Gustatory assessment on both sides of the tongue was performed using dry taste strips. RESULTS: Comparison of mean taste scores on the side of diseased ear vs normal ear was done. On the diseased side the mean taste score was 9.16 and on the normal side the mean taste score was 13.24. The difference between the two was found to be statistically significant (P < 0.0001). The results were also analyzed for various other parameters like type, duration, and location of disease. CONCLUSION: A patient with chronic inflammatory middle ear disease already has dysfunctional chorda tympani and is unlikely to notice a change in the taste sensation in the event of cutting of the nerve during the course of an ear surgery.

[Anatomical course of the chorda tympani nerve in middle ear surgery: clinical classification and relevance for postoperative gustatory dysfunction]. / Verlauf der Chorda tympani bei Operationen des Mittelohres: Klinische Einteilung und ihre Bedeutung für postoperative Schmeckstörungen.

BACKGROUND: The anatomical course of the Chorda tympani nerve (CTN) in the middle ear is known to be very variable, which becomes most obvious during middle ear operations. As well, postoperative gustatory dysfunction belongs to the most frequent complications after otosurgical interventions. The aim of this study was to develop a clinical classification of the intraoperatively visible course of the CTN and to demonstrate a possible correlation of its anatomic course with the prevalence of actual postoperative taste disorders. METHODS: Only cases of first-time ear surgery all operated by one experienced otosurgeon were assessed. Preoperatively, gustatory testing with standardised chemical solutions (sweet, sour, salty, bitter) was performed. During surgery the course of the CTN was classified at first sight by 3 topografical criteria: The angle (A), the height (H) and the depth (D) of the nerve's emergence from the lateral tympanic wall. In cases of postoperative taste dysfunction the patients were followed-up on a regular basis. RESULTS: 103 patients were included in the study. The angle of the nerve;s emergence from the tympanic bone was below 30 degrees in 59 (A1), between 30 degrees and 60 degrees in 41 (A2) and within 60 degrees and 90 degrees in 3 cases (A3). The height of emergence was 33 times in the superior (H1), 61 times in the middle (H2) and 9 times in the inferior third (H3) of the posterior meatal wall. The depth of emergence lay within the plain of the tympanic sulcus in 26 individuals (D1), 44 times medially to this plain without overlapping bone (D2) and 33 times medially but covered by a bony spur (D3). The CTN was preserved in 92 procedures. Postoperatively, gustatory function was diminished in 7% of the cases. CONCLUSION: This study confirms the high diversity of the surgical anatomy of the CTN. According to the proposed classification the A1-H1-D2/3-situation belongs to the CTN-constellations observed most frequently. It is this very anatomical situation, that apparently tends to be associated with postoperative taste deficits quite regularly due to inevitable intraoperative manipulations. Taking into account the results of this study an otosurgeon might be able to anticipate the potential risk for the CTN by judging the AHD-status intraoperatively and - therefore - reduce taste disorders postoperatively. Additionally, the probability of a postoperative gustatory dysfunction depends upon the kind of underlying middle ear disease as well.

Regenerative Failure Following Rat Neonatal Chorda Tympani Transection is Associated with Geniculate Ganglion Cell Loss and Terminal Field Plasticity in the Nucleus of the Solitary Tract.

Neural insult during development results in recovery outcomes that vary dependent upon the system under investigation. Nerve regeneration does not occur if the rat gustatory chorda tympani nerve is sectioned (CTX) during neonatal (≤P10) development. It is unclear how chorda tympani soma and terminal fields are affected after neonatal CTX. The current study determined the impact of neonatal CTX on chorda tympani neurons and brainstem gustatory terminal fields. To assess terminal field volume in the nucleus of the solitary tract (NTS), rats received CTX at P5 or P10 followed by chorda tympani label, or glossopharyngeal (GL) and greater superficial petrosal (GSP) label as adults. In another group of animals, terminal field volumes and numbers of chorda tympani neurons in the geniculate ganglion (GG) were determined by labeling the chorda tympani with DiI at the time of CTX in neonatal (P5) and adult (P50) rats. There was a greater loss of chorda tympani neurons following P5 CTX compared to adult denervation. Chorda tympani terminal field volume was dramatically reduced 50 days after P5 or P10 CTX. Lack of nerve regeneration after neonatal CTX is not caused by ganglion cell death alone, as approximately 30% of chorda tympani neurons survived into adulthood. Although the total field volume of intact gustatory nerves was not altered, the GSP volume and GSP-GL overlap increased in the dorsal NTS after CTX at P5, but not P10, demonstrating age-dependent plasticity. Our findings indicate that the developing gustatory system is highly plastic and simultaneously vulnerable to injury.

Taste deficits after middle ear surgery for otosclerosis: taste somatosensory interactions.

The aim of this study was to evaluate the postoperative consequences of chorda tympani reclining during middle ear surgery for otosclerosis. Electrogustometric taste thresholds were measured at 11 loci on the tongue and the soft palate in 14 patients before surgery, and 8 d, 1 month and (in some cases) 6 months after surgery. A significant increase in thresholds was observed on the ipsilateral side of the tongue after surgery. The extent of the deficit and the recovery time course depended on tongue locus. The tip of the tongue displayed a limited deficit, suggesting bilateral chorda tympani innervation. The edge of the tongue was less impaired than the dorsal or the lateral tip loci; it may be dually innervated by both chorda tympani and glossopharyngeal nerves in humans, as already shown in rats. Likewise for the fungiform papillae located just anterior to the circumvallate papillae. Somatosensory early complaints suggest a derepression of chorda tympani on lingual nerve signals. In a second stage, relief of complaints before electrogustometric threshold recovery suggested trigeminal compensation of the chorda tympani deficit. Relief of complaints seems to involve central integrative processes, whereas the evolution of electrogustometric threshold represents the actual recovery time course of chorda tympani peripheral sensitivity.

Change of somatosensory function of the tongue caused by chorda tympani nerve disorder after stapes surgery.

OBJECTIVES: Patients after middle ear surgery often complain of taste disturbance and a lingual numbness. The purpose of this study was to objectively assess changes in the somatosensation of the tongue and taste function in patients undergoing stapes surgery. STUDY DESIGN: Prospective study. METHODS: Symptoms of taste disturbance and tongue numbness after surgery were investigated before and after surgery in 41 patients (13 males, 28 females; mean age 41.8 years) who underwent stapes surgery. Twenty-eight patients (9 males, 19 females; mean age 43.1 years) underwent sensory and taste function tests before and after surgery. Sensory function of the tongue was measured at the operated side and the nonoperated side using the 2-point discrimination test and an electrostimulator test. Taste function was assessed with electrogustometry (EGM). RESULTS: The chorda tympani nerve (CTN) was gently touched or stretched in all patients. Postoperative thresholds on the operated side were significantly higher than preoperative thresholds in all tests in the patients who underwent all three kinds of tests. Tongue somatosensory symptoms improved significantly earlier than the taste disturbance postoperatively, and the sensory thresholds returned to the baseline along with recovery of symptoms. CONCLUSION: These findings suggest that dysfunction of the CTN occurred following surgery even when the CTN was preserved, and that the sensory nerve threshold of the tongue correlated with the symptom of lingual numbness. The CTN may play a role not only in taste function but also in the somatosensory function of the tongue. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:701-706, 2018.

Dystonin deficiency reduces taste buds and fungiform papillae in the anterior part of the tongue.

The anterior part of the tongue was examined in wild type and dystonia musculorum mice to assess the effect of dystonin loss on fungiform papillae. In the mutant mouse, the density of fungiform papillae and their taste buds was severely decreased when compared to wild type littermates (papilla, 67% reduction; taste bud, 77% reduction). The mutation also reduced the size of these papillae (17% reduction) and taste buds (29% reduction). In addition, immunohistochemical analysis demonstrated that the dystonin mutation reduced the number of PGP 9.5 and calbindin D28k-containing nerve fibers in fungiform papillae. These data together suggest that dystonin is required for the innervation and development of fungiform papillae and taste buds.

Upregulation of the chemokine monocyte chemoattractant protein-1 following unilateral nerve injury in the peripheral taste system.

Macrophages are recruited to both sides of the tongue following unilateral chorda tympani (CT) nerve injury. The mechanisms responsible for recruiting these macrophages to the peripheral taste system are unknown. Neural degeneration in other systems leads to the upregulation of small molecules that function as chemoattractant cytokines, or chemokines. The chemokines monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha are important regulators of macrophage recruitment to sites of infection and injury. We hypothesized that CT nerve sectioning leads to a bilateral upregulation of MCP-1 and MIP-1alpha. We examined lingual protein levels of MCP-1 and MIP-1alpha by enzyme-linked immunosorbent assays (ELISA)s at several time points after unilateral CT section in rats. MCP-1 was significantly upregulated on the intact side of the tongue at 12 h after sectioning, and on the injured side at 24-48 h post-injury. However, MIP-1alpha expression did not significantly change following CT nerve sectioning. These data indicate that chemokines are differentially regulated following neural injury, and that MCP-1 may contribute to the bilateral macrophage response to neural injury. Furthermore, the increase in MCP-1 occurs even in uninjured, distant sites, and may be upstream from the deficits in neural responses from the contralateral CT after sectioning.

Impact of Jacobson's (tympanic) nerve sectioning on middle ear functions.

OBJECTIVE: The purpose of this study was to evaluate the influence of sectioning of the Jacobson's (tympanic) nerve on middle ear functions. METHOD: Twenty-five adult New Zealand rabbits were included in this study. The Jacobson's nerve was cut in the left ear of the rabbits (study group), whereas only a small mucosal incision was performed while keeping the Jacobson's nerve intact in their right ear (control group). After the operation, the ears were assessed both otomicroscopically and histopathologically on Days 30, 60, and 90. RESULTS: On otomicroscopy, retraction pockets were observed in 48 and 4% of the ears in the study and control groups, respectively (p < 0.001). Middle ear effusion was observed in 56 and 12%, respectively (p < 0.01). Histopathologically, an inflammation in the middle ear mucosa was present in all ears in the study group, whereas it was present only in 20% of the control ears (p < 0.001). Goblet cells were observed in 48 and 20% in the study and control groups, respectively (p < 0.04). In the study group, the otomicroscopic and histopathologic findings were more prominent on Day 60 compared to Day 90 (p < 0.05). CONCLUSION: Tympanic glomus cells seem to act as middle ear chemosensory organs and are involved in the regulation of middle ear aeration. Disruption of these neural elements such as Jacobson's nerve negatively impacts on middle ear functions and may result in atelectasis.