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Scientific Reports Jan 2024Nasal obstruction exerts considerable physiological effects on the respiratory system and craniofacial morphology during the developmental stage. This study used...
Nasal obstruction exerts considerable physiological effects on the respiratory system and craniofacial morphology during the developmental stage. This study used MMP-3-LUC transgenic rats for in vivo tracking of long-term expression in the rat nasal region after unilateral nasal obstruction. Skeletal changes of the craniofacial, nasal, and sinus regions were measured through micro-computed tomography examination and analysis with 3D image processing and calculation. Matrix metalloproteinase-3 and olfactory marker protein expression were also investigated through immunohistochemistry (IHC). Unilateral nasal obstruction significantly reduced the MMP-3 signal in the nasal region of MMP-3-LUC transgenic rats, which was mainly expressed in the respiratory epithelium. Long-term obstruction also caused morphological changes of the craniofacial hard tissue, such as nasal septal deviation, longer inter-jaw distance, and increased maxillary molar dental height. It also caused compensatory growth in olfactory nerve bundles and the olfactory epithelium, as confirmed by IHC. In our study, long-term unilateral nasal obstruction caused nasal septal deviation toward the unobstructed side, hyper divergent facial development including longer molar dental height, and reduced MMP-3 production. However, further investigation is necessary to explore the mechanism in depth.
Topics: Rats; Animals; Nasal Obstruction; Rats, Transgenic; Matrix Metalloproteinase 3; X-Ray Microtomography; Nasal Septum; Animals, Laboratory
PubMed: 38297007
DOI: 10.1038/s41598-024-51544-3 -
Frontiers in Neurology 2023SARS-CoV-2 infection can affect any organ, including both the central nervous system (CNS) and peripheral nervous system (PNS). The aim of this study was to explore the...
INTRODUCTION
SARS-CoV-2 infection can affect any organ, including both the central nervous system (CNS) and peripheral nervous system (PNS). The aim of this study was to explore the outcome and risk factors associated with the involvement of either CNS or PNS in a cohort of hospitalized COVID-19 patients.
METHODS
We performed a retrospective observational cohort study of hospitalized adult patients with COVID-19, between May 2020 and December 2022, presenting with new onset neurological disabilities any time after admission.
RESULTS
We included 115 patients, 72 with CNS manifestations and 43 with PNS involvement. The CNS manifestations were COVID-19-associated encephalopathy, headache, neurovascular events, and seizures in 80.5, 43, 31.9, and 11.1% of patients, respectively. The neurovascular events were ischemic stroke in 17 (23.6%) patients, hemorrhagic stroke in 6 (8.3%) patients, venous thrombosis in 1 (1.4%) patient, and subarachnoid hemorrhage in 1 (1.4%) patient. Cranial nerve involvement was the most frequent PNS manifestation in 34 (79%) cases, followed by mononeuritis in 5 (11.6%) patients and polyneuropathy in 4 (9.3%) patients. The affected cranial nerves were the vestibulocochlear nerve in 26 (60.5%) patients, the olfactory nerve in 24 (55.8%) patients, the oculomotor nerves in 5 (11.6%) patients, and the facial nerve in 1 (2.3%) patient. Two patients (9.3%) presented with polyneuritis cranialis. Older age (HR = 1.02, 95% CI: 1.003-1.037, = 0.01), COVID severity (HR = 2.53, 95% CI: 1.42-4.5, = 0.002), ischemic cardiac disease (HR = 2.42, 95% CI: 1.05-5.6, = 0.03), and increased D-dimers (HR = 1.00, 95% CI: 1.00-1.00, = 0.02) were independently associated with the development of CNS manifestations. The factors associated with in-hospital mortality were age (HR = 1.059, 95% CI: 1.024-1.096, = 0.001), C-reactive protein (HR = 1.006, 95% CI: 1.00-1.011, = 0.03), CNS involvement (HR = 9.155, 95% CI: 1.185-70.74, = 0.03), and leucocyte number (HR = 1.053, 95% CI: 1.026-1.081, < 0.001).
CONCLUSION
COVID-19-associated encephalopathy was the most common CNS manifestation in our study, but neurovascular events are also important considering the overlap between inflammatory and prothrombotic pathways, especially in severe cases. CNS involvement was associated with in-hospital all-cause mortality. PNS findings were various, involving mostly the cranial nerves, especially the vestibulocochlear nerve.
PubMed: 38274890
DOI: 10.3389/fneur.2023.1338593 -
International Journal of Molecular... Jan 2024Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote...
Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.
Topics: Humans; Culture Techniques; Anti-Bacterial Agents; Axons; Biological Transport; Mesenchymal Stem Cells
PubMed: 38255817
DOI: 10.3390/ijms25020743 -
Pathogens (Basel, Switzerland) Dec 2023Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of...
Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.
PubMed: 38251344
DOI: 10.3390/pathogens13010037 -
ENeuro Feb 2024Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation...
Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily in sensory cortices. Nevertheless, emerging evidence emphasizes its significance in sensory organs and in subcortical regions where cranial nerves relay information to the brain. Additionally, critical questions started to arise. Do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry points? Does the deprivation duration correlate with specific plasticity mechanisms? This study systematically reviews and meta-analyzes research papers that investigated visual, auditory, or olfactory deprivation in rodents of both sexes. It examines the consequences of sensory deprivation in homologous regions at the first central synapse following cranial nerve transmission (vision - lateral geniculate nucleus and superior colliculus; audition - ventral and dorsal cochlear nucleus; olfaction - olfactory bulb). The systematic search yielded 91 papers (39 vision, 22 audition, 30 olfaction), revealing substantial heterogeneity in publication trends, experimental methods, measures of plasticity, and reporting across the sensory modalities. Despite these differences, commonalities emerged when correlating plasticity mechanisms with the duration of sensory deprivation. Short-term deprivation (up to 1 d) reduced activity and increased disinhibition, medium-term deprivation (1 d to a week) involved glial changes and synaptic remodeling, and long-term deprivation (over a week) primarily led to structural alterations. These findings underscore the importance of standardizing methodologies and reporting practices. Additionally, they highlight the value of cross-modal synthesis for understanding how the nervous system, including peripheral, precortical, and cortical areas, respond to and compensate for sensory inputs loss.
Topics: Male; Animals; Female; Rodentia; Hearing; Synaptic Transmission; Synapses; Vision, Ocular; Neuronal Plasticity; Sensory Deprivation
PubMed: 38195533
DOI: 10.1523/ENEURO.0435-23.2023 -
Neurochemical Research Apr 2024Dysfunctional sensory systems, including altered olfactory function, have recently been reported in patients with autism spectrum disorder (ASD). Disturbances in...
Dysfunctional sensory systems, including altered olfactory function, have recently been reported in patients with autism spectrum disorder (ASD). Disturbances in olfactory processing can potentially result from gamma-aminobutyric acid (GABA)ergic synaptic abnormalities. The specific molecular mechanism by which GABAergic transmission affects the olfactory system in ASD remains unclear. Therefore, the present study aimed to evaluate selected components of the GABAergic system in olfactory brain regions and primary olfactory neurons isolated from Shank3-deficient () mice, which are known for their autism-like behavioral phenotype. Shank3 deficiency led to a significant reduction in GEPHYRIN/GABAR colocalization in the piriform cortex and in primary neurons isolated from the olfactory bulb, while no change of cell morphology was observed. Gene expression analysis revealed a significant reduction in the mRNA levels of GABA transporter 1 in the olfactory bulb and Collybistin in the frontal cortex of the Shank3 mice compared to WT mice. A similar trend of reduction was observed in the expression of Somatostatin in the frontal cortex of Shank3 mice. The analysis of the expression of other GABAergic neurotransmission markers did not yield statistically significant results. Overall, it appears that Shank3 deficiency leads to changes in GABAergic synapses in the brain regions that are important for olfactory information processing, which may represent basis for understanding functional impairments in autism.
Topics: Humans; Mice; Animals; Autism Spectrum Disorder; Nerve Tissue Proteins; Neurons; Synapses; gamma-Aminobutyric Acid; Olfactory Cortex; Microfilament Proteins
PubMed: 38183586
DOI: 10.1007/s11064-023-04097-2 -
Frontiers in Cellular Neuroscience 2023Vomeronasal sensory neurons (VSNs) recognize pheromonal and kairomonal semiochemicals in the lumen of the vomeronasal organ. VSNs send their axons along the vomeronasal...
Vomeronasal sensory neurons (VSNs) recognize pheromonal and kairomonal semiochemicals in the lumen of the vomeronasal organ. VSNs send their axons along the vomeronasal nerve (VN) into multiple glomeruli of the accessory olfactory bulb (AOB) and form glutamatergic synapses with apical dendrites of mitral cells, the projection neurons of the AOB. Juxtaglomerular interneurons release the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Besides ionotropic GABA receptors, the metabotropic GABA receptor has been shown to modulate synaptic transmission in the main olfactory system. Here we show that GABA receptors are expressed in the AOB and are primarily located at VN terminals. Electrical stimulation of the VN provokes calcium elevations in VSN nerve terminals, and activation of GABA receptors by the agonist baclofen abolishes calcium influx in AOB slice preparations. Patch clamp recordings reveal that synaptic transmission from the VN to mitral cells can be completely suppressed by activation of GABA receptors. A potent GABA receptor antagonist, CGP 52432, reversed the baclofen-induced effects. These results indicate that modulation of VSNs via activation of GABA receptors affects calcium influx and glutamate release at presynaptic terminals and likely balances synaptic transmission at the first synapse of the accessory olfactory system.
PubMed: 38130867
DOI: 10.3389/fncel.2023.1302955 -
ELife Dec 2023The joint storage and reciprocal retrieval of learnt associated signals are presumably encoded by associative memory cells. In the accumulation and enrichment of memory...
The joint storage and reciprocal retrieval of learnt associated signals are presumably encoded by associative memory cells. In the accumulation and enrichment of memory contents in lifespan, a signal often becomes a core signal associatively shared for other signals. One specific group of associative memory neurons that encode this core signal likely interconnects multiple groups of associative memory neurons that encode these other signals for their joint storage and reciprocal retrieval. We have examined this hypothesis in a mouse model of associative learning by pairing the whisker tactile signal sequentially with the olfactory signal, the gustatory signal, and the tail-heating signal. Mice experienced this associative learning show the whisker fluctuation induced by olfactory, gustatory, and tail-heating signals, or the other way around, that is, memories to multi-modal associated signals featured by their reciprocal retrievals. Barrel cortical neurons in these mice become able to encode olfactory, gustatory, and tail-heating signals alongside the whisker signal. Barrel cortical neurons interconnect piriform, S1-Tr, and gustatory cortical neurons. With the barrel cortex as the hub, the indirect activation occurs among piriform, gustatory, and S1-Tr cortices for the second-order associative memory. These associative memory neurons recruited to encode multi-modal signals in the barrel cortex for associative memory are downregulated by knockdown. Thus, associative memory neurons can be recruited as the core cellular substrate to memorize multiple associated signals for the first-order and the second-order of associative memories by neuroligin-3-mediated synapse formation, which constitutes neuronal substrates of cognitive activities in the field of memoriology.
Topics: Animals; Mice; Neurons; Cell Adhesion Molecules, Neuronal; Nerve Tissue Proteins; Synapses
PubMed: 38047770
DOI: 10.7554/eLife.87969 -
Brain Imaging and Behavior Apr 2024Traumatic axonal injury (TAI) may result in the disruption of brain functional networks and is strongly associated with cognitive impairment. However, the neural...
Traumatic axonal injury (TAI) may result in the disruption of brain functional networks and is strongly associated with cognitive impairment. However, the neural mechanisms affecting the neurocognitive function after TAI remain to be elucidated. We collected the resting-state functional magnetic resonance imaging data from 28 patients with TAI and 28 matched healthy controls. An automated anatomical labeling atlas was used to construct a functional brain connectome. We utilized a graph theoretical approach to investigate the alterations in global and regional network topologies, and network-based statistics analysis was utilized to localize the connected networks more precisely. The current study revealed that patients with TAI and healthy controls both showed a typical small-world topology of the functional brain networks. However, patients with TAI exhibited a significantly lower local efficiency compared to healthy controls, whereas no significant difference emerged in other small-world properties (Cp, Lp, γ, λ, and σ) and global efficiency. Moreover, patients with TAI exhibited aberrant nodal centralities in some regions, including the frontal lobes, parietal lobes, caudate nucleus, and cerebellum bilaterally, and right olfactory cortex. The network-based statistics results showed alterations in the long-distance functional connections in the subnetwork in patients with TAI, involving these brain regions with significantly altered nodal centralities. These alterations suggest that brain networks of individuals with TAI present aberrant topological attributes that are associated with cognitive impairment, which could be potential biomarkers for predicting cognitive dysfunction and help understanding the neuropathological mechanisms in patients with TAI.
Topics: Humans; Male; Adult; Magnetic Resonance Imaging; Brain; Female; Connectome; Neural Pathways; Nerve Net; Middle Aged; Young Adult; Diffuse Axonal Injury
PubMed: 38044412
DOI: 10.1007/s11682-023-00832-z -
Pediatric and Developmental Pathology :... 2024Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically...
Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically have variable degree of developmental delay or intellectual disability, muscular hypotonia, dysmorphic facial features, sparse scalp hair, but otherwise hirsutism and fifth digit nail or distal phalanx hypoplasia or aplasia. Coffin-Siris syndrome is caused by pathogenic variants in 12 different genes including and . Pathogenic gene variants cause Coffin-Siris syndrome 3 whereas pathogenic gene variants cause Coffin-Siris syndrome 2. Here, we present two prenatal Coffin-Siris syndrome cases with autosomal dominant pathogenic variants: gene c.1066_1067del, p.(Leu356AspfsTer4) variant, and a novel gene c.1920+3_1920+6del variant. The prenatal phenotype in Coffin-Siris syndrome has been rarely described. This article widens the phenotypic spectrum of prenatal Coffin-Siris syndrome with severely hypoplastic right ventricle with VSD and truncus arteriosus type III, persisting left superior and inferior caval vein, bilateral olfactory nerve aplasia, and hypoplastic thymus. A detailed clinical description of the patients with ultrasound, MRI, and pictures of the affected fetuses showing the wide phenotypic spectrum of the disease is presented.
Topics: Humans; Intellectual Disability; Abnormalities, Multiple; Face; Phenotype; Hand Deformities, Congenital; Micrognathism; Neck
PubMed: 37981638
DOI: 10.1177/10935266231210155