Olfactory Bulb Atrophy Research Articles

Pediatric neuroimaging findings and clinical presentations of COVID-19: A systematic review

ObjectivesSymptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children. MethodsA literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients. ResultsA total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis. ConclusionRadiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p<0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p<0.05, from whole brain statistical parametric map analysis). This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies. This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case.

Magnetic Resonance Imaging Scan of the Brain After Mild COVID-19 Infection.

There have been several reports of central nervous system impairments associated with severe coronavirus disease 2019 (COVID-19) infection on head magnetic resonance imaging and angiography (MRI/A). However, head MRI/A is rarely performed in mild cases, and there have been few reports on intracranial changes after COVID-19 infection in these cases. Here, we report a comparative examination of the findings seen in common head MRI/A sequences in mild cases of COVID-19. Of the 15,376 patients who underwent head MRI/A examination called "Brain Dock"between June 2020 and June 2021, 746 patients who received a COVID-19 antibody test were evaluated. Positive and negative patients were comparatively examined for head MRI/A findings such as cerebral white matter lesions, ischemic changes, cerebral microbleeds, cerebral aneurysms, arterial stenosis, sinusitis, and other abnormal findings. Overall, 31 (4.2%) patients were COVID-19 positive, and all of them had mild infections not requiring hospitalization. There was no significant difference in patient characteristics and head MRI/A findings between positive and negative patients. All positive patients showed no particular abnormalities in the nasal findings such as olfactory bulb atrophy or thickening of the olfactory mucosa. Intracranial lesions in mild patients do not show a clear difference from those in negative patients. This indicates that findings seen in common MRI/A sequences of severe patients are not likely in mild patients, supporting that there is relatively no damage to the central nervous system in mild patients.

MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms.

Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated yet. Brain MR imaging is a consolidated method for evaluating olfactory system's morphological modification, but a few quantitative studies have been published so far. The aim of the study was to provide MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms, including olfactory dysfunction. 196 COVID-19 patients (median age: 53years, 56% females) and 39 controls (median age 55years, 49% females) were included in this cross-sectional observational study; 78 of the patients reported olfactory loss as the only neurological symptom. MRI processing was performed by ad-hoc semi-automatic processing procedures. Olfactory bulb (OB) volume was measured on T2-weighted MRI based on manual tracing and normalized to the brain volume. Olfactory tract (OT) median signal intensity was quantified on fluid attenuated inversion recovery (FLAIR) sequences, after preliminary intensity normalization. COVID-19 patients showed significantly lower left, right and total OB volumes than controls (p < 0.05). Age-related OB atrophy was found in the control but not in the patient population. No significant difference was found between patients with olfactory disorders and other neurological symptoms. Several outliers with abnormally high OT FLAIR signal intensity were found in the patient group. Brain MRI findings demonstrated OB damage in COVID-19 patients with neurological complications. Future longitudinal studies are needed to clarify the transient or permanent nature of OB atrophy in COVID-19 pathology.

Olfactory Bulb Integrity in Frontotemporal Dementia and Alzheimer’s Disease

Olfactory dysfunction is highly prevalent in dementia syndromes, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). The structural integrity of the olfactory bulb (OB) is thought to play a critical role in odor detection and identification, but no MRI study has measured OB volume in FTD, or measured OB volume longitudinally in AD. To measure OB volume in FTD and AD patients longitudinally using MRI. This study measured OB volumes using MRI in patients diagnosed with behavioral-variant FTD (n = 55), semantic dementia (n = 34), progressive non-fluent aphasia (n = 30), AD (n = 50), and healthy age-matched controls (n = 55) at their first visit to a dementia research clinic ('baseline'). Imaging data in patients 12-months later were analyzed where available (n = 84) for longitudinal assessment. Volumes of subcortical and cortical olfactory regions ('olfactory network') were obtained via surface-based morphometry. Results revealed that in AD and FTD at baseline, OB volumes were similar to controls, whereas volumes of olfactory network regions were significantly reduced in all patient groups except in progressive non-fluent aphasia. Longitudinal data revealed that OB volume became significantly reduced (10-25% volume reduction) in all dementia groups with disease progression. Olfactory dysfunction is common in patients diagnosed with AD or FTD, but our results indicate that there is no detectable volume loss to the OBs upon first presentation to the clinic. Our findings indicate that the OBs become detectably atrophied later in the disease process. OB atrophy indicates the potential usefulness for OBs to be targeted in interventions to improve olfactory function.

Lewy Body Disease Primate Model with α-Synuclein Propagation from the Olfactory Bulb.

Lewy body diseases (LBDs), which are pathologically defined as the presence of intraneuronal α-synuclein (α-Syn) inclusions called Lewy bodies, encompass Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Autopsy studies have shown that the olfactory bulb (OB) is one of the regions where Lewy pathology develops and initiates its spread in the brain. This study aims to clarify how Lewy pathology spreads from the OB and affects brain functions using nonhuman primates. We inoculated α-Syn preformed fibrils into the unilateral OBs of common marmosets (Callithrix jacchus) and performed pathological analyses, manganese-enhanced magnetic resonance imaging, and 18 F-fluoro-2-deoxy-d-glucose positron emission tomography up to 6months postinoculation. Severe α-Syn pathology was observed within the olfactory pathway and limbic system, while mild α-Syn pathology was seen in a wide range of brain regions, including the substantia nigra pars compacta, locus coeruleus, and even dorsal motor nucleus of the vagus nerve. The brain imaging analyses showed reduction in volume of the OB and progressive glucose hypometabolism in widespread brain regions, including the occipital lobe, and extended beyond the pathologically affected regions. We generated a novel nonhuman primate LBD model with α-Syn propagation from the OB. This model suggests that α-Syn propagation from the OB is related to OB atrophy and cerebral glucose hypometabolism in LBDs. © 2022 International Parkinson and Movement Disorder Society.

Bilateral Olfactory Bulb Atrophy in Post-COVID-19 Parosmia.

Here, read about a case of persistent parosmia in an elderly women with MRI findings of bilateral olfactory bulb atrophy, supporting a neuronal mechanism for persisting olfactory symptoms among COVID-19 survivors.

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.

α-synuclein propagation via olfactory pathway induces olfactory bulb atrophy and widespread glucose hypometabolism in a non-human primate model. (P1-1.Virtual)

α-synuclein propagation via olfactory pathway induces olfactory bulb atrophy and widespread glucose hypometabolism in a non-human primate model. (P1-1.Virtual)

The olfactory bulb - gateway for SARS-Cov-2?

Introduction. Anosmia and ageusia are one of the most common and characteristic symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, with a frequency of almost 50% in patients in Western countries. Hypotheses proposing that the virus potentially affects the central nervous system (CNS) are on the rise. One hypothesis suggests that the virus enters via nasal mucosa and then enters the olfactory bulb via cribriform plate, with further dissemination to the CNS. Case report. A 34-year-old female patient experienced the loss of the sense of smell and taste about two months before testing positive for SARS-Cov-2. Coronavirus disease 2019 (COVID-19) presented with minor pneumonia and worsening anosmia and ageusia. After treatment, the patient recovered well, but anosmia and ageusia appeared again, varying in intensity, and since February 2021, they have become persistent. The case was evaluated by an otorhino-laryngologist, pulmonologist, and finally, a neurologist. In the meantime, the patient tested negative for SARS-Cov-2 and received two doses of the Sputnik V vaccine. Brain magnetic resonance imaging (MRI) was performed, and it clearly showed severe bilateral olfactory bulb atrophy. The patient has had anosmia and ageusia up to this day, and future MRI follow-up is planned. Conclusion. Loss of sense of smell and taste may be a predictor of further CNS dis-semination of the virus and possible neurological complications (which is still a subject of consideration). The olfactory bulb could be a gateway to COVID-19 intrusion into the CNS, and its atrophy could be an indicator of the process. Further investigation on this topic is required, including a wide application of MRI, in order to come to definite conclusions.

Diet enriched in omega-3 fatty acids alleviates olfactory system deficits in APOE4 transgenic mice.

Olfactory dysfunction is observed in several neurological disorders including Mild Cognitive Impairment (MCI) and Alzheimer disease (AD). These deficits occur early and correlate with global cognitive performance, depression and degeneration of olfactory regions in the brain. Despite extensive human studies, there has been little characterization of the olfactory system in models of AD. In order to determine if olfactory structural and/or molecular phenotypes are observed in a model expressing a genetic risk factor for AD, we assessed the olfactory bulb (OB) in APOE4 transgenic mice. A significant decrease in OB weight was observed at 12 months of age in APOE4 mice concurrent with inflammation and decreased NeuN expression. In order to determine if a diet rich in omega-3s may alleviate the olfactory system phenotypes observed, we assessed WT and APOE4 mice on a docosahexaenoic acid (DHA) diet. APOE4 mice on a DHA diet did not present with atrophy of the OB, and the alterations in NeuN and IBA-1 expression were alleviated. Furthermore, alterations in caspase mRNA and protein expression in the APOE4 OB were not observed with a DHA diet. Similar to the human AD condition, OB atrophy is an early phenotype in the APOE4 mice and concurrent with inflammation. These data support a link between the structural olfactory brain region atrophy and the olfactory dysfunction observed in AD and suggest that inflammation and cell death pathways may contribute to the olfactory deficits observed. Furthermore, the results suggest that diets enriched in DHA may provide benefit to APOE4 allele carriers.

Effect of olfactory bulb atrophy on the success of olfactory training.

To evaluate the success of olfactory training in patients with olfactory loss and olfactory bulb (OB) atrophy detected on magnetic resonance imaging (MRI) and other characteristics. This study included 48 patients with olfactory loss who underwent a nasal endoscopic examination and MRI before olfactory training. The Korean Version of the Sniffin' Sticks Test was performed before and after training. The olfactory training success was defined as an improvement of more than 6 points in the Threshold-Discrimination-Identification (TDI) score. Patient characteristics and OB atrophy pre-training were compared between successful and unsuccessful groups. The etiology of olfactory loss included respiratory viral infection in 30 (62.5%), trauma in 10 (20.8%), and idiopathic loss in 8 (16.7%) patients. Twenty-three (47.9%) of 48 patients exhibited successful olfactory training. Etiology, age, gender, and symptom duration were not different between unsuccessful and successful groups. Pre-training discrimination, identification, and TDI scores were significantly different between unsuccessful and successful groups (P < 0.05). Success rate of patients with bilateral OB atrophy was significantly lower than that of patients with unilateral OB atrophy and normal morphology (P = 0.006). OB height was significantly lower in the unsuccessful group than in the successful group (P < 0.05). Bilateral OB atrophy was an independent risk factor for failure of olfactory training according to the multivariate analysis. Olfactory loss patients with bilateral OB atrophy may not be able to improve olfactory function after olfactory training.

Differential Effects of Nasal Inflammation and Odor Deprivation on Layer-Specific Degeneration of the Mouse Olfactory Bulb.

Harmful environmental agents cause nasal inflammation, and chronic nasal inflammation induces a loss of olfactory sensory neurons (OSNs) and reversible atrophy of the olfactory bulb (OB). Here, we investigated the mechanisms underlying this inflammation-induced OB atrophy by histologically and biochemically comparing the OB changes in mouse models of nasal inflammation and odor deprivation. In addition, we examined whether odor stimulation is necessary for OB recovery from atrophy. One group of adult male C57BL/6 mice was administered lipopolysaccharide (LPS) unilaterally for 10 weeks to induce nasal inflammation (control animals received saline), and a second group received unilateral naris closures (NCs) for 10 weeks of odor deprivation. The OBs atrophied in both models, but odor deprivation shrank the glomerular, external plexiform, mitral, and granule cell layers (GCLs), whereas the olfactory nerve, glomerular, and external plexiform layers (EPLs) atrophied as a result of nasal inflammation. Additionally, nasal inflammation, but not odor deprivation, caused neuroinflammation in the OB, inducing glial activation and elevated expression of interleukin-1β (IL-1β) and TNFα. After 10 weeks of nasal inflammation, mice were housed for another 10 weeks with no additional treatment or with unilateral NC. Nasal inflammation and glial activation subsided in both groups, but glomerular and EPLs recovered only in those with no additional treatment. Our findings demonstrate that nasal inflammation and odor deprivation differentially induce layer-specific degeneration in the OB, that loss of OSN activity rather than neuroinflammation is a major cause of inflammation-induced OB atrophy, and that odor stimulation is required for OB recovery from atrophy.

An investigation of olfactory bulb and entorhinal cortex volumes in both patients with Alzheimer's disease and healthy individuals, and a comparative analysis of neuropeptides

Alzheimer’s Disease (AD) is the most common neurodegenerative disease and is hard to diagnose at the early stages. The pathogenesis of AD is associated with the loss of a sense of smell. Reduction in the volumes of the Olfactory Bulb (OB) and Entorhinal Cortex (EC) is positively correlated with the decline of the smelling function where OB projects to EC. This study aims to detect the early changes in OB and EC volumes in AD patients by comparing them to healthy subjects. This study also aims to make a comparative analysis of plasma levels and the relationship between arginine-vasopressin (AVP) and Oxytocin (OT), which are neuropeptides associated with cognitive functions. The participants comprised 9 AD patients and 12 healthy individuals. We used volumetric methods such as MRICloud and IBASPM to measure the OB and EC volumes with the help of 3D MRI (Magnetic Resonance Imaging) images. We compared the left and right differentiation. Moreover, we investigated the neuropeptide levels in blood samples from the participants. We conducted a correlation analysis for all parameters. Bilateral OB atrophy was discovered in the AD patients in comparison to the control group (p=0.002 for right; p=0.015 for left). The right OB volume was measured to be larger than the left OB volume in the control group,but this asymmetry was not observed in the AD patients. The right and left EC's of the AD patients were atrophic in comparison to the control (p

Olfactory bulb atrophy and caspase activation observed in the BACHD rat models of Huntington disease

Olfactory dysfunction is observed in several neurological disorders, including Huntington disease (HD), and correlates with global cognitive performance, depression and degeneration of olfactory regions in the brain. Despite clear evidence demonstrating olfactory dysfunction in HD patients, only limited details are available in murine models and the underlying mechanisms are unknown. In order to determine if alterations in the olfactory bulb (OB) are observed in HD we assessed OB weight or area from 3 to 12 months of age in the BACHD transgenic lines (TG5 and TG9). A significant decrease in the OB was observed at 6 and 12 months of age compared to WT. We also detected increased mRNA and protein expression of mutant huntingtin (mHTT) in the OB of TG5 compared to TG9 at specific ages. Despite the higher expression of mHTT in the TG5 OBs, there was increased nuclear accumulation of mHTT in the OB of TG9 compared to WT and TG5 rats. As we observed atrophy of the OB in the BACHD rats we assessed for caspase activation, a known mechanism underlying the cell death observed in HD. We characterized caspase-3, −6, −8 and − 9 mRNA and protein expression levels in the OB of the BACHD transgenic lines at 3, 6 and 12 months of age. Alterations in caspase mRNA and protein expression were detected in the TG5 and TG9 lines. However, the changes observed in the mRNA and protein levels are in some cases discordant, suggesting that the caspase protein modifications detected may be more attributable to post-translational modifications. The caspase activation studies support that cell death may be increased in the rodent HD OB and further our understanding of the olfactory dysfunction and the role of caspases in the pathogenesis of HD.

Abstract # 2045 Nasal inflammatory stage-associated plastic changes in the olfactory bulb neurocircuit

We are exposed to harmful environmental agents that may cause nasal inflammation. Although prolonged nasal inflammation results in long-lasting olfactory loss, little is known about the influence of chronic nasal inflammation on the olfactory bulb (OB). We made a mouse model of chronic nasal inflammation by repeatedly administering lipopolysaccharide (LPS) to nostril and histologically analyzed changes in the olfactory epithelium (OE) and OB. Mice received LPS or saline every other day (3 times per week) for 3, 10, 18 or 24 weeks. For the recovery analyses, the mice treated with LPS for 10 weeks were housed without treatment for another 10 weeks. LPS induced OE inflammation with a loss of olfactory sensory neurons (OSNs). More than 10 weeks of LPS administration caused robust OB atrophy with a complete loss of OSNs. In atrophied OB, a prominent shrinkage occurred in the external plexiform layer (EPL) in addition to the olfactory nerve and glomerular layers. The superficial layer of the EPL, in which tufted cells form dendrodendritic synapses with interneurons, underwent shrinkage in a selective manner, although neither tufted cells nor interneurons underwent cell death. The atrophied OB returned to the normal size after the 10-week period of no treatment. These indicate a particular OB circuit, in which tufted cells are involved, is vulnerable to a chronic nasal inflammation but retains high plasticity to recover from atrophy.

Olfactory bulb atrophy in migraine patients.

Osmophobia and headache triggered by odors are commonly seen in migraine, and these are symptoms that differentiate migraine from other primary headaches. Since these odor-related symptoms are disease-specific, we aimed to measure the volume of olfactory bulb and depth of olfactory sulcus in migraine patients. A total of 93 subjects, consisting of 62 episodic migraine (32 with osmophobia, 30 without osmophobia) patients and 31 healthy controls, were included in this study. Diagnosis and classification of migraine were performed according to the beta version criteria of International Classification of Headache Disorders (ICHD-3 Beta version). Beck depression and beck anxiety inventory were applied to the patients, and the measurement of bilateral olfactory bulb volume (OBV) and olfactory sulcus depth (OSD) was performed manually in the brain magnetic resonance imaging (MRI). More significantly in the left OBV, low OBV has been determined in migraine patients compared to the control group (p < 0.001, p = 0.020). When migraine patients with or without osmophobia were compared to the control group; OBV was determined to be the lowest in migraine group with osmophobia, and left-weighted bilateral OBV was determined to be low (p < 0.001, p = 0.046). No statistically significant difference was determined between groups in OSD measurements (p = 0.646, p = 0.490). Left-weighted bilateral OBV atrophy determined in migraine patients may be guiding for the clarification of migraine pathophysiology and enlightening of the relation between migraine and odor.

MR Imaging-Based Evaluations of Olfactory Bulb Atrophy in Patients with Olfactory Dysfunction.

Although the olfactory bulb volume as assessed with MR imaging is known to reflect olfactory function, it is not always measured during olfactory pathway assessments in clinical settings. We aimed to evaluate the utility of visual olfactory bulb atrophy and neuropathy analyses using MR imaging in patients with olfactory dysfunction. Thirty-four patients who presented with subjective olfactory loss between March 2016 and February 2017 were included. Patients underwent a nasal endoscopic examination, olfactory testing with the Korean Version of the Sniffin' Sticks test, and MR imaging. All patients completed the Sino-Nasal Outcome Test and Questionnaire of Olfactory Disorders. Olfactory bulb atrophy and neuropathy were evaluated on MR images by 2 head and neck radiologists. The etiology of olfactory loss was chronic rhinosinusitis with/without nasal polyps in 15 (44.1%) patients, respiratory viral infection in 7 (20.6%), trauma in 2 (5.9%), and idiopathic in 10 (29.4%) patients. Although 10 (29.4%) of the 34 patients were normosmic according to the Sniffin' Sticks test, their scores on the other tests were like those of patients who were hyposmic/anosmic according to the Sniffin' Sticks test. However, the detection rate of olfactory bulb atrophy was significantly higher in patients with hyposmia/anosmia than it was in patients with normosmia (P = .002). No difference in olfactory bulb neuropathy was identified among patients with normosmia and hyposmia/anosmia (P = .395). MR imaging evaluations of olfactory bulb atrophy can be used to objectively diagnose olfactory dysfunction in patients with subjective olfactory loss.

The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis

Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis (MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS. In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale (EDSS) score 3.0 (range 0-7.5), 103 relapsing-remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging (MRI); data of 27 healthy people served as age- and gender-matched control subjects. The olfactory bulb was semi-automatically segmented on high-resolution three-dimensional T1-weighted MRI. Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 ± 40.1 vs. 209.2 ± 59.3 μl; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = -0.38, P < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing-remitting MS. Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS.

Minocycline Restores Olfactory Bulb Volume and Olfactory Behavior after Traumatic Brain Injury in Mice

Permanent olfactory dysfunction can often arise after traumatic brain injury (TBI) and while one of the main causes is the immediate loss of neurons in the olfactory bulb (OB), the emergent neuroinflammatory environment following TBI may further promote OB deterioration. Therefore, we examined the effects of acute anti-inflammatory treatment with minocycline on post-TBI olfactory behavior and on OB surface. The mouse model of closed-head injury by mechanical percussion was applied to anesthetized Swiss mice. The treatment protocol included three injections of minocycline (i.p.) at 5 min (90 mg/kg), 3 h, and 9 h (45 mg/kg) post-TBI. An olfactory avoidance test was run up to 12 weeks post-TBI. The mice were then sacrificed and their OB surface was measured. Our results demonstrated a post-TBI olfactory behavior deficit that was significant up to at least 12 weeks post-TBI. Additionally, substantial post-TBI OB atrophy was observed that was strongly correlated with the behavioral impairment. Minocycline was able to attenuate both the olfactory lesions and corresponding functional deficit in the short and long term. These results emphasize the potential role of minocycline as a promising neuroprotective agent for the treatment of TBI-related olfactory bulb lesions and deficits.