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Explore (New York, N.Y.) 2023This study aimed to investigate the effect of short-term inhalation of fir essential oil on autonomic nervous activity in middle-aged women. Twenty-six women (mean age,... (Clinical Trial)
Clinical Trial
This study aimed to investigate the effect of short-term inhalation of fir essential oil on autonomic nervous activity in middle-aged women. Twenty-six women (mean age, 51.0 ± 2.9 years) participated in this study. The participants sat on a chair, closed their eyes, and inhaled fir essential oil and room air (control) for 3 min. A crossover trial was performed to eliminate the effect of the order of olfactory stimulation. Approximately half of the participants were administered stimuli in the following order: exposure to fir essential oil, then control. The remaining participants were administered control, followed by fir essential oil. Heart rate variability, heart rate, blood pressure, and pulse rate were used as indicators of the autonomic nervous system activity. The Semantic Differential method and Profile of Mood States were used as psychological indicators. The High Frequency (HF) value, an indicator of parasympathetic nerve activity reflecting a relaxed state, was significantly higher during stimulation with fir essential oil than during the control condition. The Low Frequency (LF)/(LF+HF) value, an indicator of sympathetic nerve activity reflecting awake state, was marginally lower during stimulation with fir essential oil than during the control condition. No significant differences were found in heart rate, blood pressure, and pulse rate. After inhaling fir essential oil, "comfortable," "relaxed," and "natural" feelings improved, negative moods decreased, and positive moods increased. In conclusion, inhalation of fir essential oil can help menopausal women in their physiological and psychological relaxation.
Topics: Female; Humans; Middle Aged; Affect; Autonomic Nervous System; Emotions; Heart Rate; Oils, Volatile; Parasympathetic Nervous System; Cross-Over Studies
PubMed: 37120331
DOI: 10.1016/j.explore.2023.04.006 -
Viruses Mar 2023There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute...
Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.
BACKGROUND
There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms.
METHODS
We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria.
RESULTS
All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%).
CONCLUSIONS
Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.
Topics: Humans; Aged; COVID-19; SARS-CoV-2; White Matter; Preexisting Condition Coverage; Nervous System Diseases; Cognitive Dysfunction; Neuritis
PubMed: 37112888
DOI: 10.3390/v15040908 -
Current Biology : CB Apr 2023The central nervous system (CNS) of chordates, including humans, develops as a hollow tube with ciliated walls containing cerebrospinal fluid. However, most of the... (Review)
Review
The central nervous system (CNS) of chordates, including humans, develops as a hollow tube with ciliated walls containing cerebrospinal fluid. However, most of the animals inhabiting our planet do not use this design and rather build their centralized brains from non-epithelialized condensations of neurons called ganglia, with no traces of epithelialized tubes or liquid-containing cavities. The evolutionary origin of tube-type CNSs stays enigmatic, especially as non-epithelialized ganglionic-type nervous systems dominate the animal kingdom. Here, I discuss recent findings relevant to understanding the potential homologies and scenarios of the origin, histology and anatomy of the chordate neural tube. The nerve cords of other deuterostomes might relate to the chordate neural tube at histological, developmental and cellular levels, including the presence of radial glia, layered stratification, retained epithelial features, morphogenesis via folding and formation of a lumen filled with liquid. Recent findings inspire a new view of hypothetical evolutionary scenarios explaining the tubular epithelialized structure of the CNS. One such idea suggests that early neural tubes were key for improved directional olfaction, which was facilitated by the liquid-containing internal cavity. The later separation of the olfactory portion of the tube led to the formation of the independent olfactory and posterior tubular CNS systems in vertebrates. According to an alternative hypothesis, the thick basiepithelial nerve cords could provide deuterostome ancestors with additional biomechanical support, which later improved by turning the basiepithelial cord into a tube filled with liquid - a hydraulic skeleton.
Topics: Animals; Humans; Neural Tube; Chordata; Biological Evolution; Vertebrates; Central Nervous System
PubMed: 37098338
DOI: 10.1016/j.cub.2023.03.045 -
BMC Immunology Apr 2023Coevolution between pathogens and their hosts decreases host morbidity and mortality. Bats host and can tolerate viruses which can be lethal to other vertebrate orders,...
BACKGROUND
Coevolution between pathogens and their hosts decreases host morbidity and mortality. Bats host and can tolerate viruses which can be lethal to other vertebrate orders, including humans. Bat adaptations to infection include localized immune response, early pathogen sensing, high interferon expression without pathogen stimulation, and regulated inflammatory response. The immune reaction is costly, and bats suppress high-cost metabolism during torpor. In the temperate zone, bats hibernate in winter, utilizing a specific behavioural adaptation to survive detrimental environmental conditions and lack of energy resources. Hibernation torpor involves major physiological changes that pose an additional challenge to bat-pathogen coexistence. Here, we compared bat cellular reaction to viral challenge under conditions simulating hibernation, evaluating the changes between torpor and euthermia.
RESULTS
We infected the olfactory nerve-derived cell culture of Myotis myotis with an endemic bat pathogen, European bat lyssavirus 1 (EBLV-1). After infection, the bat cells were cultivated at two different temperatures, 37 °C and 5 °C, to examine the cell response during conditions simulating euthermia and torpor, respectively. The mRNA isolated from the cells was sequenced and analysed for differential gene expression attributable to the temperature and/or infection treatment. In conditions simulating euthermia, infected bat cells produce an excess signalling by multitude of pathways involved in apoptosis and immune regulation influencing proliferation of regulatory cell types which can, in synergy with other produced cytokines, contribute to viral tolerance. We found no up- or down-regulated genes expressed in infected cells cultivated at conditions simulating torpor compared to non-infected cells cultivated under the same conditions. When studying the reaction of uninfected cells to the temperature treatment, bat cells show an increased production of heat shock proteins (HSPs) with chaperone activity, improving the bat's ability to repair molecular structures damaged due to the stress related to the temperature change.
CONCLUSIONS
The lack of bat cell reaction to infection in conditions simulating hibernation may contribute to the virus tolerance or persistence in bats. Together with the cell damage repair mechanisms induced in response to hibernation, the immune regulation may promote bats' ability to act as reservoirs of zoonotic viruses such as lyssaviruses.
Topics: Animals; Chiroptera; Hibernation; Lyssavirus; Transcriptome; Viruses
PubMed: 37085747
DOI: 10.1186/s12865-023-00542-7 -
Neurobiology of Disease Jun 2023Olfactory ensheathing cells (OECs) serve as a bridge by migrating at the site of spinal cord injury (SCI) to facilitate the repair of the neural structure and neural...
BACKGROUND
Olfactory ensheathing cells (OECs) serve as a bridge by migrating at the site of spinal cord injury (SCI) to facilitate the repair of the neural structure and neural function. However, OEC migration at the injury site not only faces the complex and disordered internal environment but also is closely associated with the migration ability of OECs.
METHODS
We extracted OECs from the olfactory bulb of SD rats aged <7 days old. We verified the micro ribonucleic acid (miR)-145a-5p expression level in the gene chip after SCI and OEC transplantation using quantitative reverse transcription (qRT)-polymerase chain reaction (PCR). The possible target gene Plexin-A2 of miR-145a-5p was screened using bioinformatics and was verified using dual-luciferase reporter assay, Western blot, and qRT-PCR. The effect of miR-145a-5p/plexin-A2 on OEC migration ability was verified by wound healing assay, Transwell cell migration assay, and immunohistochemistry. Nerve repair was observed at the injured site of the spinal cord after OEC transplantation using tissue immunofluorescence and magnetic resonance imaging, diffusion tensor imaging, and the Basso-Beattie-Bresnahan locomotor rating scale were further used for imaging and functional evaluation.
RESULTS
miR-145a-5p expression in the injured spinal cord tissue after SCI considerably decreased, while Plexin-A2 expression significantly increased. OEC transplantation can reverse miR-145a-5p and Plexin-A2 expression after SCI. miR-145a-5p overexpression enhanced the intrinsic migration ability of OECs. As a target gene of miR-145a-5p, Plexin-A2 hinders OEC migration. OEC transplantation overexpressing miR-145a-5p after SCI can increase miR-145a-5p levels in the spinal cord, reduce Plexin-A2 expression in the OECs and the spinal cord tissue, and promote OEC migration and distribution at the injured site. OEC transplantation overexpressing miR-145a-5p can promote the repair of neural morphology and neural function.
CONCLUSIONS
Our study demonstrated that miR-145a-5p could promote OEC migration by down-regulating the target gene Plexin-A2, and transplantation of miR-145a-5p engineered OECs was beneficial to enhance neural structural and functional recovery in SCI rats.
Topics: Rats; Animals; Rats, Sprague-Dawley; Diffusion Tensor Imaging; Spinal Cord Injuries; Olfactory Bulb; MicroRNAs
PubMed: 37068642
DOI: 10.1016/j.nbd.2023.106129 -
EBioMedicine May 2023Routes along the olfactory nerves crossing the cribriform plate that extend to lymphatic vessels within the nasal cavity have been identified as a critical cerebrospinal...
BACKGROUND
Routes along the olfactory nerves crossing the cribriform plate that extend to lymphatic vessels within the nasal cavity have been identified as a critical cerebrospinal fluid (CSF) outflow pathway. However, it is still unclear how the efflux pathways along the nerves connect to lymphatic vessels or if any functional barriers are present at this site. The aim of this study was to anatomically define the connections between the subarachnoid space and the lymphatic system at the cribriform plate in mice.
METHODS
PEGylated fluorescent microbeads were infused into the CSF space in Prox1-GFP reporter mice and decalcification histology was utilized to investigate the anatomical connections between the subarachnoid space and the lymphatic vessels in the nasal submucosa. A fluorescently-labelled antibody marking vascular endothelium was injected into the cisterna magna to demonstrate the functionality of the lymphatic vessels in the olfactory region. Finally, we performed immunostaining to study the distribution of the arachnoid barrier at the cribriform plate region.
FINDINGS
We identified that there are open and direct connections from the subarachnoid space to lymphatic vessels enwrapping the olfactory nerves as they cross the cribriform plate towards the nasal submucosa. Furthermore, lymphatic vessels adjacent to the olfactory bulbs form a continuous network that is functionally connected to lymphatics in the nasal submucosa. Immunostainings revealed a discontinuous distribution of the arachnoid barrier at the olfactory region of the mouse.
INTERPRETATION
Our data supports a direct bulk flow mechanism through the cribriform plate allowing CSF drainage into nasal submucosal lymphatics in mice.
FUNDING
This study was supported by the Swiss National Science Foundation (310030_189226), Dementia Research Switzerland-Synapsis Foundation, the Heidi Seiler Stiftung and the Fondation Dr. Corinne Schuler.
Topics: Animals; Mice; Olfactory Nerve; Ethmoid Bone; Lymphatic System; Subarachnoid Space; Lymphatic Vessels
PubMed: 37043871
DOI: 10.1016/j.ebiom.2023.104558 -
Frontiers in Neurology 2023Inverted papilloma (IP) and nasal polyp (NP), as two benign lesions, are difficult to distinguish on MRI imaging and clinically, especially in predicting whether the...
BACKGROUND AND PURPOSE
Inverted papilloma (IP) and nasal polyp (NP), as two benign lesions, are difficult to distinguish on MRI imaging and clinically, especially in predicting whether the olfactory nerve is damaged, which is an important aspect of treatment and prognosis. We plan to establish a new biomarker to distinguish IP and NP that may invade the olfactory nerve, and to analyze its diagnostic efficacy.
MATERIALS AND METHODS
A total of 74 cases of IP and 55 cases of NP were collected. A total of 80% of 129 patients were used as the training set (59 IP and 44 NP); the remaining were used as the testing set. As a multimodal study (two MRI sequences and clinical indicators), preoperative MR images including T2-weighted magnetic resonance imaging (T2-WI) and contrast-enhanced T1-weighted magnetic resonance imaging (CE-T1WI) were collected. Radiomic features were extracted from MR images. Then, the least absolute shrinkage and selection operator (LASSO) regression method was used to decrease the high degree of redundancy and irrelevance. Subsequently, the radiomics model is constructed by the rad scoring formula. The area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the model have been calculated. Finally, the decision curve analysis (DCA) is used to evaluate the clinical practicability of the model.
RESULTS
There were significant differences in age, nasal bleeding, and hyposmia between the two lesions ( < 0.05). In total, 1,906 radiomic features were extracted from T2-WI and CE-T1WI images. After feature selection, using 12 key features to bulid model. AUC, sensitivity, specificity, and accuracy on the testing cohort of the optimal model were, respectively, 0.9121, 0.828, 0.9091, and 0.899. AUC on the testing cohort of the optimal model was 0.9121; in addition, sensitivity, specificity, and accuracy were, respectively, 0.828, 0.9091, and 0.899.
CONCLUSION
A new biomarker combining multimodal MRI radiomics and clinical indicators can effectively distinguish between IP and NP that may invade the olfactory nerve, which can provide a valuable decision basis for individualized treatment.
PubMed: 37025198
DOI: 10.3389/fneur.2023.1151455 -
PloS One 2023There is increasing evidence of both central and peripheral nervous system (PNS) involvement in COVID-19. We conducted this systematic literature review to investigate...
There is increasing evidence of both central and peripheral nervous system (PNS) involvement in COVID-19. We conducted this systematic literature review to investigate the characteristics, management and outcomes of patients with PNS, including the types and severity of cranial nerves (CN) involvement. We systematically searched on PubMed for studies reporting adult patients diagnosed with COVID-19 and PNS involvement until July 2021. From 1670 records, 225 articles matched the inclusion criteria, with a total of 1320 neurological events, in 1004 patients. There were 805 (61%) CN, 350 (26.5%) PNS, and 165 (12.5%) PNS plus CN events. The most frequently involved CN were the facial, vestibulo-cochlear and olfactory nerve in 27.3%, 25.4% and 16.1%, respectively. Guillain-Barre syndrome spectrum was identified in 84.2% of PNS events. We analysed 328 patients reported in 225 articles with CN, PNS, and PNS plus CN involvement. The patients with CN involvement were younger (mean age 46.2±17.1, p = .003), and were more frequently treated as outpatients (p < .001), mostly with glucocorticoids (p < .001). Patients that had PNS with or without CN involvement were more likely to be hospitalized (p < .001), and to receive intravenous immunoglobulins (p = .002) or plasma exchange (p = .002). Patients with CN, PNS, and PNS plus CN had severe COVID -19 disease in 24.8%, 37.3%, 34.9% respectively. The most common neurological outcome was mild/moderate sequelae in patients with CN, PNS, and PNS plus CN in 54.7%, 67.5% and 67.8% respectively (p = .1) and no significant difference was found between the three categories regarding death, disease severity, time from disease onset to neurological symptoms, lack of improvement and complete recovery. CN involvement was the most frequent PNS finding. All three categories of PNS involvement were rather associated to non-severe COVID-19 but it may be an important cause of hospitalization and post COVID-19 sequelae.
Topics: Adult; Humans; Middle Aged; COVID-19; Guillain-Barre Syndrome; Immunoglobulins, Intravenous; Plasma Exchange; Peripheral Nervous System
PubMed: 37023030
DOI: 10.1371/journal.pone.0283827 -
Cancers Mar 2023Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of...
Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System.
Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58-12.54), olfactory nerve disorders (8.02; 2.44-26.33), and hallucinations (22.96; 8.45-62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.
PubMed: 36980737
DOI: 10.3390/cancers15061851