Olfactory Nerve Injury Research Articles

Anosmia/hyposmia differences between severe acute respiratory syndrome coronavirus 2 variants; objective olfactory function evaluation

Objectives: This study aimed to investigate whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants cause more or less loss of smell than the wild type variant as a clinical finding that may guide physicians in addition to the increased mortality feature. Patients and Methods: In the prospective study, Connecticut Chemosensory Clinical Research Center (CCCRC) odor testing was performed on patients hospitalized for coronavirus disease 2019 (COVID-19) between May 2021 and December 2021, and variants of SARS-CoV-2 isolated from patients were analyzed. A total of 51 patients (30 males and 21 females; mean age 59.3±14.2 years; range, 29 to 88 years) were included in the study. Age, sex, and COVID-19 vaccine status of the patients were recorded. The patients were asked whether they had new-onset odor or taste complaints and whether they differently perceived smells they knew. Results: The delta variant was detected in 14 patients, the alpha variant was detected in 20 patients, and no variant of concern was detected in 17 patients. Odor disorders were present in 79.4% of all patients (13.73% anosmia, 15.69% severe hyposmia, 13.7% moderate hyposmia, and 37.2% mild hyposmia). There was no statistically significant difference between sex, age, smoking habits, presence of parosmia, degree of smell disorder, and Vicks definition results according to the variants (p>0.05). A statistically significant difference was found between alpha and delta variants in terms of patients' complaints of decreased smell and taste, mean olfactory threshold value, and mean olfactory score variables (p<0.05). There was no difference in terms of age and identification score. The complaints of smell and taste disorders, the mean threshold value of odor, and the mean odor score were found to be significantly lower in the delta variant than in the alpha variant. Conclusion: SARS-CoV-2 variants differ significantly in olfactory dysfunction. Future clinical and laboratory studies may show the diagnostic, clinical, and prognostic significance of olfactory nerve injury.

Using of ¹⁸F-FDG to evaluate the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway: a PET-MRI pilot study

Objective:This study evaluated the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway via the instillation of ¹⁸F-FDG at the olfactory cleft. Method:Seven healthy volunteers and 5 patients with traumatic dysosmia were enrolled in the study. Subjects were all instilled with ¹⁸F-FDG on each side of the olfactory cleft under endoscopy. After 12 hours, a PET/MR scan was performed to track the metabolism pathway of ¹⁸F-FDG. Then, we compared the diameter of the olfactory bulb and the olfactory bulb intake between normal volunteers and patients with traumatic olfactory disorders. Result:In healthy volunteers, there was a significant difference in ¹⁸F-FDG uptake between the regions of interest in which ¹⁸F-FDG was or was not in contact with the cribriform plate（P=0.012 7）; this difference also existed in patients with traumatic olfactory disorders（P=0.038 1）. Patients with traumatic olfactory disorders did not exhibit significant differences in ¹⁸F-FDG uptake in the region of interest compared with healthy volunteers（P=0.937 2）. Conclusion:The olfactory bulb is obviously atrophied in patients with traumatic olfactory dysfunction, and the uptake of ¹⁸F-FDG in the olfactory bulb region of interest is also reduced. The administration of ¹⁸F-FDG via olfactory fissure area can enter olfactory bulb and parafrontal tissues through the nasal brain pathway,¹⁸F-FDG can enter the central nervous system through the nasal-brain pathway, which is not affected by olfactory nerve transection injury.

Research progress on olfactory dysfunction of patients after endonasal transsphenoidal approach pituitary adenomas resection

This paper reviewed the incidence and recovery of olfactory dysfunction, causes of postoperative olfactory dysfunction, the influence of olfactory dysfunction on quality of life, recovery situation after olfactory nerve injury and methods of promoting olfactory recovery among patients after endonasal transsphenoidal approach pituitary adenomas resection so as to provide a basis for exploring the effective intervention further. Key words: Review; Pituitary neoplasms; Olfactory dysfunction; Endonasal transsphenoidal surgery

Clipping of paraclinoid aneurysms associated with multiple and bilateral aneurysms through contralateral pterional approach

Objective: To investigate the minimally invasive techniques and the indication of paraclinoid aneurysms associated with other aneurysms' clipping via the contralateral approach. Methods: From January 2011 to January 2015, 9 paraclinoid aneurysms associated with other aneurysms were clipped via contralateral approach at the Department of Neurosurgery, Beijing Tiantan Hospital.The records of these patients were analyzed retrospectively to review the clinical outcome and surgical skills. Results: A total of 20 multiple bilateral aneurysms (9 of contralateral paraclinoid aneurysms, 4 of ICA aneurysms, 4 of posterior communicating artery aneurysms, 2 of anterior communicating artery aneurysms and 1 of anterior cerebral artery aneurysm) from 9 patients were clipped successfully through a unilateral pterional craniotomy.All patients with paraclinoid aneurysms who underwent surgery through contralateral approach showed a good recovery.Postoperative digital subtraction angiography or computerized tomography angiography did not show any residual aneurysm.One patients had ipsilateral olfactory nerve injury during operation.One had cerebral ischemia after surgery, and other patients discharged uneventfully.Of the 1 patients with preoperative visual symptoms showed an improvement. No visual function impairment was observed among others. Conclusions: The contralateral approach remains a safe and reliable treatment option for medial directed paraclinoid aneurysms and those associated with bilateral intracranial aneurysms.For bilateral multiple aneurysms associated this kind of paraclinoid aneurysms, consideration may be given to clipping all aneurysms with the contralateral approach.

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.

Tumor necrosis factor-α antagonist suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury.

Olfactory dysfunction is a common finding in head trauma due to injury to the olfactory nerve. We previously reported that anti-inflammatory treatment with steroids improves recovery outcome in olfactory nerve injury models. Clinically, however, steroid administration is not recommended in the acute phase of head injury cases because of concerns regarding its side effects. Tumor necrosis factor (TNF-α) is known to play a key role in inflammatory response to injury. The present study examines if the inhibition of TNF-α can facilitate functional recovery in the olfactory system following injury. Olfactory nerve transection (NTx) was performed in olfactory marker protein (OMP-tau-lacZ) mice to establish injury models. We measured TNF-α gene expression in the olfactory bulb using semi-quantitative and real time polymerase chain reaction (PCR) assays and found that they increase within hours after NTx injury. A TNF-α antagonist (etanercept) was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5-70 days. 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. Etanercept-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. Olfactory function assessments using both an olfactory avoidance behavioral test and evoked potential recordings showed improved functional recovery in etanercept-injected animals. These findings suggest that inhibition of TNF-α could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

Endoscopy-assisted cerebral falx incision via unilateral approach for treatment of dissymmetric bilateral frontal contusion

ObjectiveTo investigate the clinical features and treatment strategy of dissymmetric bilateral frontal contusion, and to summarize our experience in treating these patients by minimally invasive surgery. MethodsOver the past 3 years, we have treated a total of 31 patients with dissymmetric bilateral frontal contusion using endoscopy-assisted unilateral cerebral falx incision. Other 30 patients treated by routine bilateral approaches within the same period were taken as control. ResultsSeventeen cases (54.8%) in the unilateral operation group survived and were in good condition, 8 (25.8%) had moderate disability, 4 (12.9%) had severe disability, 1 (3.2%) was in vegetative state, and 1 (3.2%) died. Compared with the control group, the Glasgow Outcome Scale score was not significantly different in the unilateral operation group, but the operation time, blood transfusion volume, the length of hospital stay, the incidences of mental disorder and olfactory nerve injury were greatly reduced in the unilateral operation group. ConclusionsEndoscopy-assisted unilateral cerebral falx incision can shorten the operation time, reduce surgical trauma and complications in treatment of patients with dissymmetric bilateral frontal contusion. It can obviously diminish the chance of delayed intracerebral hematoma and subsequently minimize the incidences of subfalcial and centrencephalic herniation.

Blockade of interleukin-6 receptor suppresses inflammatory reaction and facilitates functional recovery following olfactory system injury

We previously reported that anti-inflammatory treatment with steroids improves recovery outcome in an olfactory nerve injury model. Clinically, however, steroid administration is not recommended in the acute phase of head injury because of concerns regarding side effects and no evidence of its efficacy. Recently, it has been reported that interleukin-6 (IL-6) plays an important role in the inflammatory reaction. The present study investigates if anti-IL-6 receptor (IL-6R) antibody can facilitate functional recovery in the olfactory system following injury. Rat anti-mouse IL-6R antibody (MR16-1) was intraperitoneally injected to severe olfactory nerve injury model mice immediately after the nerve transection (NTx). Histological assessment of recovery within the olfactory bulb was made at 5–70 days. X-gal staining labeled the degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. MR16-1-injected animals showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. Olfactory function assessments using both an olfactory avoidance behavioral test and evoked potential testing showed improved functional recovery in MR16-1-injected mice. These findings suggest that blockade of IL-6R could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

Endoscopy-Assisted Cerebral Falx Incision Via Unilateral Approach in Treatment of Dissymmetric Bilateral Frontal Contusion

Dissymmetric bilateral frontal contusion (DBFC) is relatively frequent in the clinic. In this study, we aimed to investigate the development tendency, clinical features, and treatment experience of DBFC and to summarize out experience in treating these patients via minimally invasive means-endoscopy. Over the past 3 years, we have treated a total of 31 patients with DBFC using endoscopy-assisted unilateral cerebral falx incision. We used a 30-degree endoscope to observe the involvement of brain contusion and whether the brain contusions have been cleaned thoroughly. Another 30 patients treated by routine bilateral approach within the same period were taken as controls. Seventeen cases (54.8%) in the unilateral-operation group survived and were in good condition, 8 cases (25.8%) had moderate disability, and 4 cases (12.9%) had severe disability; 1 case (3.2%) was in vegetable state, and 1 case (3.2%) died. Compared with the control group, the GOS score was not significantly different in the unilateral-operation group, but the operation time, blood transfusion volume, length of hospital stay, incidence of mental disorder, and incidence of olfactory nerve injury were greatly reduced in the unilateral-operation group. Endoscopy-assisted unilateral cerebral falx incision can shorten the operation time and reduce surgical trauma and complications when used for treatment of patients with DBFC.

Olfactory Nerve Recovery Following Mild and Severe Injury and the Efficacy of Dexamethasone Treatment

To investigate factors that influence the degree of neural regeneration and recovery, we studied 2 olfactory nerve injury models. Transection of the olfactory nerves along the surface of the olfactory bulb was performed in OMP-tau-lacZ mice using either a flexible Teflon blade (mild injury) or a stainless steel blade (severe injury). Histological assessment of recovery within the olfactory bulb was made at 5, 14, and 42 days after injury. We used X-gal staining to label the degenerating and regenerating olfactory nerve fibers and immunohistochemical staining to detect the presence of reactive astrocytes and macrophages. Areas of injury-associated tissue were significantly smaller in the mild injury model, and at 42 days, the regenerated nerves had reestablished connections to the glomerular layer of the bulb. With severe injury, there were larger areas of injury-associated tissue, more astrocytes and macrophages, and a decrease in regenerated nerve fibers. When dexamethasone (DXM) was injected after severe injury, there was a significant reduction in injury-associated tissue, better nerve recovery, and fewer astrocytes and macrophages. These results demonstrate that recovery in the olfactory system varies with the severity of injury and that DXM treatment may have therapeutic value by reducing injury-associated tissue and improving recovery outcome.

Odor Detection Ability and Thallium-201 Transport in the Olfactory Nerve of Traumatic Olfactory-Impaired Mice

Although olfactory nerve damage is a contributing factor in the diagnosis of posttraumatic olfactory loss, at present, there are no methods to directly assess injury to these nerves. We have shown that following olfactory nerve injury in mice, thallium-201 (201 Tl) transport from the nasal cavity to the olfactory bulb decreases. To determine if olfactory function after nerve injury could be assessed with nasal administration of 201 Tl, we measured the correlation between odor detection ability (ODA) and the rate of transport of 201 Tl in olfactory nerves. Both ODA and 201 Tl transport were measured after bilateral olfactory nerve transection for a 4-week period. Cycloheximide solution was used for ODA against tap water. 201 Tl transport was measured as the ratio of radioactivity in the nasal cavity and olfactory bulb with gamma spectrometry. There was a significant correlation between ODA and the rate of 201 Tl transport in the olfactory nerve. These findings suggest that olfactory function after nerve injury can be objectively evaluated with the nasal administration of 201 Tl.

Peak in matrix metaloproteinases-2 levels observed during recovery from olfactory nerve injury

Matrix metalloproteineases are associated with extracellular remodeling that occurs in injury and repair processes in the central nervous system (CNS). We examined the role of MMP-2 in a model of olfactory nerve injury and found that MMP-2 levels increased several hours following injury, peaked at day 7 and then decreased rapidly. We previously reported a rapid increase in MMP-9, within 5 h after nerve injury, corresponding to neuronal degeneration and increased glial activity. In this study, we show that MMP-2 peaks later than MMP-9, at the onset of neuronal regeneration and repair. Using MMP-9 knockout mice, we determined that the MMP-2 increase is independent of MMP-9. Our data suggest that MMP-2 and MMP-9 may play different roles in the injury and repair processes.

Thallium Transport and the Evaluation of Olfactory Nerve Connectivity between the Nasal Cavity and Olfactory Bulb

Little is known regarding how alkali metal ions are transported in the olfactory nerve following their intranasal administration. In this study, we show that an alkali metal ion, thallium is transported in the olfactory nerve fibers to the olfactory bulb in mice. The olfactory nerve fibers of mice were transected on both sides of the body under anesthesia. A double tracer solution (thallium-201, (201)Tl; manganese-54, (54)Mn) was administered into the nasal cavity the following day. Radioactivity in the olfactory bulb and nasal turbinate was analyzed with gamma spectrometry. Auto radiographic images were obtained from coronal slices of frozen heads of mice administered with (201)Tl or (54)Mn. The transection of the olfactory nerve fibers was confirmed with a neuronal tracer. The transport of intranasal administered (201)Tl/(54)Mn to the olfactory bulb was significantly reduced by the transection of olfactory nerve fibers. The olfactory nerve transection also significantly inhibited the accumulation of fluoro-ruby in the olfactory bulb. Findings indicate that thallium is transported by the olfactory nerve fibers to the olfactory bulb in mice. The assessment of thallium transport following head injury may provide a new diagnostic method for the evaluation of olfactory nerve injury.

Response of matrix metalloproteinase-9 to olfactory nerve injury

Matrix metalloproteinases function in the remodeling of the extracellular matrix during growth and development as well as in injury and disease processes. We examined the role of matrix metalloproteinase-9 in a model of olfactory nerve injury in mice. We measured changes in matrix metalloproteinase-9 protein levels for up to 60 days following olfactory nerve transection. Matrix metalloproteinase-9 levels increased within hours after injury, peaked at day 1 and were elevated for approximately 2 weeks before returning to control levels over the 60-day time period. The increase in matrix metalloproteinase-9 was temporally associated with the degeneration of olfactory neurons that follows nerve transection and with increased gliosis. Our results demonstrate a temporal relationship between matrix metalloproteinase-9 elevation, degeneration of olfactory neurons and gliosis.

Microglia in the olfactory bulb of rats during postnatal development and olfactory nerve injury with zinc sulfate: a lectin labeling and ultrastrucutural study

Using isolectin (GSA I-B4) as a marker, this study examined the possible alterations of lectin-labeled membranous glycoproteins in microglial cells in the olfactory bulb of normal development and under experimentally induced degeneration. In light microscopy, several morphological types of microglial cells representing different degrees of cell differentiation were distributed in the bulb laminae. A gradient of microglial differentiation extending from the intermediate to superficial and intermediate to deep occurs in the bulb layers. The differentiation gradient and lectin labeling pattern of microglial cells in the developing bulb resembled those in other areas of the brain tissues. Differentiating microglia showed a gradual diminution of lectin staining when the nascent round cells transformed into the mature ramified cells. Microglia in the external plexiform layer of the olfactory bulb were the first to mature and the cells expressed very weak lectin reactivity. In mature or adult rats, some microglial cells showing intense lectin labeling were observed in the olfactory nerve layer, granule cell layer and subependymal layer. Ultrastructurally, lectin labeling was localized at the trans saccules of the Golgi apparatus. Microglial cells in other bulb laminae, however, exhibited a negative reaction for the isolectin at the Golgi apparatus. Following intranasal irrigation of zinc sulfate, some microglial cells in the olfactory nerve layer and glomerular layer were activated to become phagocytic cells with increased lectin labeling at their ramified processes. GSA I-B4 staining was also localized at their trans saccules of the Golgi apparatus. The lectin labeling pattern of these phagocytic cells resembled that of differentiating microglia in postnatal bulbs, suggesting that bulb microglia in the lesioned sites were activated through cell dedifferentiation into macrophages.

The immunopathology of olfactory nerve injury and hemorrhage in gerbils

Patients with head injury may experience olfactory dysfunction. Unfortunately, little is known about changes in the olfactory neuroepithellum caused by intracranial olfactory nerve injury and hemorrhage. We performed olfactory nerve section or bulbectomy in 53 Mongolian gerbils and subjected the olfactory neuroepithelium to immunohistochemical analysis. A decrease or disappearance of the antiserum to an olfactory marker protein containing olfactory receptor neurons was evident in the sectioned group. Degeneration of the olfactory neuroepithelium contralateral to olfactory nerve injury was also noted in animals with perineural hemorrhage. These findings suggest that olfactory dysfunction may occur not only with nerve injury but also secondary to intracranial hemorrhage.