-
Heliyon May 2024Both myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) are demyelinating diseases of the central...
BACKGROUND AND OBJECTIVES
Both myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) are demyelinating diseases of the central nervous system. They present similar clinical manifestations such as optica neuritis, myelitis and area postrema syndrome (APS). The distinctions of optica neuritis (ON) and myelitis between them have been elaborated to great length while their differences in APS remain to be elucidated. We aim to report the frequency of APS in patients with MOGAD as well as NNOSD patients, and to compare the characteristics of APS between patients with MOGAD and those with NMOSD.
METHODS
Seven MOG-IgG positive APS patients were retrospectively identified between 2017 and 2022. APS phenotypes have been previously described. The similarities and differences between MOGAD and NMOSD patients with APS was compared, including the frequency and duration of APS between the two diseases, and their incidences of accompanied subtentorial lesions have also been described and compared.
RESULTS
We reviewed a cohort of 218 MOG-IgG-positive patients, and 396 patients with NMOSD. 200 MOGAD patients and 332 NMOSD patients were included in this study. In the cohort, seven patients with MOG-IgG-positive antibody presented with APS were analyzed, four of whom had disease onset with APS. Of the 332 patients with NMOSD, 47 had APS attacks while 31 had APS at disease onset. In patients with MOGAD, 2 had nausea, 3 had vomiting, 5 had hiccups, and 1 patient presented with all three symptoms above. In patients with NMOSD, 70.2 % had nausea, vomiting and hiccups at the same time during APS attacks. Apart from the medulla oblongata, other subtentorial regions were also affected in 6/7 MOGAD patients while 14/47 NMOSD patients had other subtentorial regions involved. During an APS attack, the incidence of concomitant lesions in the brainstem and other regions was significantly greater in MOGAD than in the NMOSD cohort (P = 0.008*).
CONCLUSION
APS is a rare, but not isolated clinical manifestation of MOGAD. APS happened more frequently with other supratentorial and subtentorial lesions in MOGAD. The symptoms of NVH (nausea, vomiting, hiccups) tended to happen respectively in MOGAD compared with NMOSD. The phenotype or mechanism of APS in MOGAD may differ from that in NMOSD.
PubMed: 38779012
DOI: 10.1016/j.heliyon.2024.e30633 -
Frontiers in Veterinary Science 2023In veterinary medicine, magnetic resonance imaging (MRI) is widely utilized for brain imaging. But the complex structures of brain tissues can give rise to artifacts...
INTRODUCTION
In veterinary medicine, magnetic resonance imaging (MRI) is widely utilized for brain imaging. But the complex structures of brain tissues can give rise to artifacts such as partial volume averaging in conventional sequences. To address this issue, several studies about double inversion recovery (DIR) sequences have been conducted in human medicine. However, published clinical studies about brain MRI using DIR sequences in dogs are currently lacking. The purpose of this study was to evaluate the magnetic resonance features of single-slab 3D DIR sequences in the normal canine brain.
METHODS
Five healthy Beagle dogs were examined and the following pulse sequences were acquired for each: (1) spin-echo T2-weighted (T2W), (2) fluid attenuated inversion recovery (FLAIR), (3) gray matter (GM) selective, and (4) white matter (WM) selective single-slab 3D DIR sequence. For qualitative analysis, the distinction between gray and white matter of the cerebral cortex, presence and severity of the image artifacts were assessed for each pulse sequence. In addition, reconstructed images of single-slab 3D DIR sequences were qualitatively evaluated. For quantitative analysis, contrast ratios (CRs), signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the GM, WM and cerebrospinal fluid (CSF) were measured for each pulse sequence.
RESULTS AND DISCUSSION
GM selective 3D DIR was superior to T2W and FLAIR in delineating the boundaries between GM and WM in the overall brain area. Whereas WM selective 3D DIR provided better gray-white matter distinction of the cerebral cortex than T2W and FLAIR at the level of the medulla oblongata, where T2W and FLAIR images exhibited severe partial volume averaging artifacts. In general, the 3D DIR images demonstrated fewer artifacts compared to other sequences, and the reconstructed sagittal and dorsal images of these sequences maintained same spatial resolution as the original transverse images without any image degradation. Both gray and white matter selective 3D DIR sequences effectively suppressed unwanted signals, thereby providing high contrast between gray and white matter. Findings from this study could serve as a foundation for further studies on DIR sequences for the evaluation of brain diseases in dogs.
PubMed: 37529177
DOI: 10.3389/fvets.2023.1156870 -
Frontiers in Genetics 2023The brain is an extraordinarily complex organ with multiple anatomical structures involved in highly specialized functions related with behavior and physiological...
The brain is an extraordinarily complex organ with multiple anatomical structures involved in highly specialized functions related with behavior and physiological homeostasis. Our goal was to build an atlas of protein-coding gene expression in the goat brain by sequencing the transcriptomes of 12 brain regions in seven female Murciano-Granadina goats, from which three of them were 1-month pregnant. Between 14,889 (cerebellar hemisphere) and 15,592 (pineal gland) protein-coding genes were expressed in goat brain regions, and most of them displayed ubiquitous or broad patterns of expression across tissues. Principal component analysis and hierarchical clustering based on the patterns of mRNA expression revealed that samples from certain brain regions tend to group according to their position in the anterior-posterior axis of the neural tube, i.e., hindbrain (pons and medulla oblongata), midbrain (rostral colliculus) and forebrain (frontal neocortex, olfactory bulb, hypothalamus, and hippocampus). Exceptions to this observation were cerebellum and glandular tissues (pineal gland and hypophysis), which showed highly divergent mRNA expression profiles. Differential expression analysis between pregnant and non-pregnant goats revealed moderate changes of mRNA expression in the frontal neocortex, hippocampus, adenohypophysis and pons, and very dramatic changes in the olfactory bulb. Many genes showing differential expression in this organ are related to olfactory function and behavior in humans. With the exception of cerebellum and glandular tissues, there is a relationship between the cellular origin of sampled regions along the anterior-posterior axis of the neural tube and their mRNA expression patterns in the goat adult brain. Gestation induces substantial changes in the mRNA expression of the olfactory bulb, a finding consistent with the key role of this anatomical structure on the development of maternal behavior.
PubMed: 37519888
DOI: 10.3389/fgene.2023.1114749 -
Neurobiology of Stress Jul 2024High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS)...
High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS) disruptions. However, neural mechanisms underlying drinking behaviors associated with stress and ANS disruptions remain unclear. The current study aims to understand neural correlates of stress, ANS disruptions, and subsequent alcohol intake in social drinkers with risky drinking. Using functional magnetic resonance imaging (fMRI), we investigated brain and heart rate (HR) autonomic responses during brief exposure to stress, alcohol, and neutral cues utilizing a well-validated, individualized imagery paradigm in 48 social drinkers of which 26 reported high-risk drinking (HD) while 22 reported low-risk drinking (LD) patterns. Results indicated that HD individuals showed stress and ANS disruptions with increased basal HR, stress-induced craving, and decreased brain response to stress exposure in frontal-striatal regions including the ventromedial prefrontal cortex (VmPFC), anterior cingulate cortex, striatum, insula, and temporal gyrus. Furthermore, whole-brain correlation analysis indicated that greater basal HR was associated with hypoactive VmPFC, but hyperactive medulla oblongata (MOb) responses during stress, with an inverse association between activity in the VmPFC and Mob (whole-brain corrected (WBC), p < 0.05). Functional connectivity with the MOb as a seed to the whole brain indicated that HD versus LD had decreased functional connectivity between the VmPFC and MOb during stress (WBC, p < 0.05). In addition, those with more compromised functional connectivity between the VmPFC and MOb during stress consumed greater amount of alcohol beverage during an experimental alcohol taste test conducted on a separate day, as well as in their self-reported weekly alcohol intake. Together, these results indicate that stress-related, dysfunctional VmPFC control over brain regions of autonomic arousal contributes to greater alcohol motivation and may be a significant risk factor for hazardous alcohol use in non-dependent social drinkers. Findings also suggest that restoring VmPFC integrity in modulating autonomic arousal during stress may be critical for preventing the development of AUD.
PubMed: 38933283
DOI: 10.1016/j.ynstr.2024.100645 -
Life Sciences Sep 2023Brown adipose tissue (BAT) can produce heat by metabolizing glucose and fatty acids. Activation of BAT is controlled by the central nervous system (CNS) through...
AIMS
Brown adipose tissue (BAT) can produce heat by metabolizing glucose and fatty acids. Activation of BAT is controlled by the central nervous system (CNS) through sympathetic innervation. Dysregulation of signalling molecules in selective CNS areas such as the nucleus of tractus solitarius (NTS) are linked with altered BAT activity, obesity and diabetes. High-fat diet (HFD)-feeding increases mitochondrial fragmentation in the NTS, triggering insulin resistance, hyperphagia and weight gain. Here we sought to determine whether changes in mitochondrial dynamics in the NTS can affect BAT glucose uptake.
MAIN METHODS
Rats received DVC stereotactic surgery for local brain administration of viruses that express mutated Drp1 genes. BAT glucose uptake was measured with PET/CT scans. Biochemical assays and immunohistochemistry determined altered levels of key signalling molecules and neural innervation of BAT.
KEY FINDINGS
We show that short-term HFD-feeding decreases BAT glucose uptake. However, inhibiting mitochondrial fragmentation in NTS-astrocytes of HFD-fed rats partially restores BAT glucose uptake accompanied by lower blood glucose and insulin levels. Tyrosine Hydroxylase (TH) revealed that rats with inhibited mitochondrial fragmentation in NTS astrocytes had higher levels of catecholaminergic innervation in BAT compared to HFD-fed rats, and did not exhibit HFD-dependent infiltration of enlarged white fat droplets in the BAT. In regular chow-fed rats, increasing mitochondrial fragmentation in the NTS-astrocytes reduced BAT glucose uptake, TH immune-positive boutons and β3-adrenergic receptor levels.
SIGNIFICANCE
Our data suggest that targeting mitochondrial dynamics in the NTS-astrocytes could be a beneficial strategy to increase glucose utilization and protect from developing obesity and diabetes.
Topics: Rats; Animals; Adipose Tissue, Brown; Solitary Nucleus; Mitochondrial Dynamics; Positron Emission Tomography Computed Tomography; Obesity; Glucose; Diet, High-Fat
PubMed: 37423379
DOI: 10.1016/j.lfs.2023.121922 -
Endocrinology and Metabolism (Seoul,... Oct 2023Insulin is a peptide hormone that regulates post-prandial physiology, and it is well known that insulin controls homeostasis at least in part via the central nervous...
BACKGRUOUND
Insulin is a peptide hormone that regulates post-prandial physiology, and it is well known that insulin controls homeostasis at least in part via the central nervous system. In particular, insulin alters the activity of neurons within the autonomic nervous system. However, currently available data are mostly from unidentified brainstem neurons of the dorsal motor nucleus of the vagus nerve (DMV).
METHODS
In this study, we used several genetically engineered mouse models to label distinct populations of neurons within the brainstem and the spinal cord for whole-cell patch clamp recordings and to assess several in vivo metabolic functions.
RESULTS
We first confirmed that insulin directly inhibited cholinergic (parasympathetic preganglionic) neurons in the DMV. We also found inhibitory effects of insulin on both the excitatory and inhibitory postsynaptic currents recorded in DMV cholinergic neurons. In addition, GABAergic neurons of the DMV and nucleus tractus solitarius were inhibited by insulin. However, insulin had no effects on the cholinergic sympathetic preganglionic neurons of the spinal cord. Finally, we obtained results suggesting that the insulininduced inhibition of parasympathetic preganglionic neurons may not play a critical role in the regulation of glucose homeostasis and gastrointestinal motility.
CONCLUSION
Our results demonstrate that insulin inhibits parasympathetic neuronal circuitry in the brainstem, while not affecting sympathetic neuronal activity in the spinal cord.
Topics: Mice; Animals; Insulin; Vagus Nerve; Neurons; Brain Stem; Cholinergic Agents
PubMed: 37749826
DOI: 10.3803/EnM.2023.1725 -
Viruses Dec 2023SARS-CoV-2 is a respiratory virus with neurological complications including the loss of smell and taste, headache, and confusion that can persist for months or longer....
BACKGROUND
SARS-CoV-2 is a respiratory virus with neurological complications including the loss of smell and taste, headache, and confusion that can persist for months or longer. Severe neuronal cell damage has also been reported in some cases. The objective of this study was to compare the infectivity of the wild-type virus, Delta (B.1.617.2) and Omicron (B.1.1.529) variants in transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2) receptor under the control of the keratin 18 promoter (K18) and characterize the progression of infection and inflammatory response in the lungs, brain, medulla oblongata, and olfactory bulbs of these animals. We hypothesized that wild type, Delta and Omicron differentially infect K18-hACE2 mice, thereby inducing distinct cellular responses.
METHODS
K18-hACE2 female mice were intranasally infected with wild-type, Delta, or Omicron variants and euthanized either at 3 days post-infection (dpi) or at the humane endpoint. None of the animals infected with the Omicron variant reached the humane endpoint and were euthanized at day 8 dpi. Virological and immunological analyses were performed in the lungs, brains, medulla oblongata and olfactory bulbs isolated from infected mice.
RESULTS
At 3 dpi, mice infected with wild type and Delta displayed significantly higher levels of viral RNA in the lungs than mice infected with Omicron, while in the brain, Delta and Omicron resulted in higher levels of viral RNA than with the wild type. Viral RNA was also detected in the medulla oblongata of mice infected by all these virus strains. At this time point, the mice infected with wild type and Delta displayed a marked upregulation of many inflammatory markers in the lungs. On the other hand, the upregulation of inflammatory markers was observed only in the brains of mice infected with Delta and Omicron. At the humane endpoint, we observed a significant increase in the levels of viral RNA in the lungs and brains of mice infected with wild type and Delta, which was accompanied by the elevated expression of many inflammatory markers. In contrast, mice which survived infection with the Omicron variant showed high levels of viral RNA and the upregulation of cytokine and chemokine expression only in the lungs at 8 dpi, suggesting that infection and inflammatory response by this variant is attenuated in the brain. Reduced RNA levels and the downregulation of inflammatory markers was also observed in the medulla oblongata and olfactory bulbs of mice infected with Omicron at 8 dpi as compared with mice infected with wild-type and Delta at the humane end point. Collectively, these data demonstrate that wild-type, Delta, and Omicron SARS-CoV-2 induce distinct levels of infection and inflammatory responses in K18-hACE2 mice. Notably, sustained brain infection accompanied by the upregulation of inflammatory markers is a critical outcome in mice infected with wild type and Delta but not Omicron.
Topics: Animals; Female; Humans; Mice; Angiotensin-Converting Enzyme 2; COVID-19; Keratin-18; Mice, Transgenic; RNA, Viral; SARS-CoV-2
PubMed: 38257760
DOI: 10.3390/v16010060 -
International Journal For Parasitology.... Aug 2023Parasites, especially brain-encysting trematodes, can have an impact on host behaviour, facilitating the transmission to next host and completion of the life cycle, but...
Parasites, especially brain-encysting trematodes, can have an impact on host behaviour, facilitating the transmission to next host and completion of the life cycle, but insufficient research has been done on whether specific brain regions are targeted. Using as a laboratory model, the precise distribution of metacercariae in experimentally-infected, wild and farmed fish was mapped. The brain regions targeted by this parasite were explored, also from a histologic perspective, and potential pathogenic effects were evaluated. Experimental infections allowed to reproduce the natural infection intensity of , with four times higher infection intensity at the higher dose (150 50 cercariae). The observed metacercarial distribution, similar among all fish groups, may reflect a trematode species-specific pattern: metacercariae occur with highest density in the optic lobe area (primarily infecting the periventricular gray zone of optic tectum) and the medulla oblongata, whereas other areas such as the olfactory lobes and cerebellar lobes may be occupied when the more frequently invaded parts of the brain were crowded. Mono- and multicysts (i.e. formed either with a single metacercaria, or with 2-25 metacercariae encapsulated together) may be formed depending on the aggregation and timing of metacercariae arrival, with minor host inflammatory response. Larvae of colonizing specific brain areas may have an effect on the functions associated with these areas, which are generally related to sensory and motor functions, but are also related to other host fitness traits such as school maintenance or recognition of predators. The detailed information on the extent and distribution of in fish encephalon sets the ground to understand the effects of brain parasites on fish, but further investigation to establish if , through purely mechanical damage (e.g., occupation, pressure and displacement), has an actual impact on host behaviour remains to be tested under controlled experimental conditions.
PubMed: 37081833
DOI: 10.1016/j.ijppaw.2023.03.004 -
Folia Morphologica Nov 2023The foramen magnum is a centralised structure found at the base of the skull. This orifice is a passageway that allows secondary structures, such as the medulla...
BACKGROUND
The foramen magnum is a centralised structure found at the base of the skull. This orifice is a passageway that allows secondary structures, such as the medulla oblongata and meninges, to pass through. The occipital condyles is a small structure on either side of the foramen magnum, forming the craniovertebral joint. The hypoglossal canal is an orifice located on the occipital canal, providing a passageway for hypoglossal nerves. The study aimed to document the morphology and morphometry of the foramen magnum, occipital condyles and hypoglossal canals within a South African population.
MATERIALS AND METHODS
Fifty skulls (n=50) were randomly selected from the Department of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal. This study investigated the morphological and morphometric parameters of the foramen magnum, occipital condyles and hypoglossal canal. The morphometric parameters were measured using a digital Vernier calliper. The data was statistically analysed using SPSS, and a p-value of <0.05 was deemed statistically significant.
RESULTS
The mean length and width of the foramen magnum was found to be 35.19mm and 27.77mm, respectively. The mean index of the foramen magnum was 1.3, which indicated that the foramen magnum was predominantly oval-shaped within the selected sample. The occipital condyles have a mean length and width of 21.73mm and 12.87mm, respectively. Furthermore, the most prevalent shape of the occipital condyles was oval. The mean length and width of the hypoglossal canals were 5.14mm and 3.87mm, respectively. While the most prevalent shape of the hypoglossal canal was oval and round on the right and left sides, respectively.
CONCLUSIONS
The findings of this study may assist in reducing the risk of injury and mortalities during trans-condylar approach procedures.
PubMed: 37957931
DOI: 10.5603/fm.95734 -
Nature Communications Feb 2024Spinal cord injury disrupts the descending command from the brain and causes a range of motor deficits. Here, we use optogenetic tools to investigate the functional...
Spinal cord injury disrupts the descending command from the brain and causes a range of motor deficits. Here, we use optogenetic tools to investigate the functional plasticity of the glutamatergic reticulospinal drive of the medullary reticular formation after a lateral thoracic hemisection in female mice. Sites evoking stronger excitatory descending drive in intact conditions are the most impaired after injury, whereas those associated with a weaker drive are potentiated. After lesion, pro- and anti-locomotor activities (that is, initiation/acceleration versus stop/deceleration) are overall preserved. Activating the descending reticulospinal drive improves stepping ability on a flat surface of chronically impaired injured mice, and its priming enhances recovery of skilled locomotion on a horizontal ladder. This study highlights the resilience and capacity for reorganization of the glutamatergic reticulospinal command after injury, along with its suitability as a therapeutical target to promote functional recovery.
Topics: Mice; Animals; Female; Neurons; Spinal Cord Injuries; Medulla Oblongata; Reticular Formation; Brain; Spinal Cord; Locomotion
PubMed: 38378819
DOI: 10.1038/s41467-024-45300-4