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BioMed Research International 2021Damage and regeneration naturally occur in the peripheral nervous system. The neurotropic B vitamins thiamine (B1), pyridoxine (B6), and cobalamin (B12) are key players,... (Review)
Review
Damage and regeneration naturally occur in the peripheral nervous system. The neurotropic B vitamins thiamine (B1), pyridoxine (B6), and cobalamin (B12) are key players, which maintain the neuronal viability in different ways. Firstly, they constantly protect nerves against damaging environmental influences. While vitamin B1 acts as a site-directed antioxidant, vitamin B6 balances nerve metabolism, and vitamin B12 maintains myelin sheaths. However, nerve injury occurs at times, because of an imbalance between protective factors and accumulating stress and noxae. This will result in the so-called Wallerian degeneration process. The presence of vitamins B1, B6, and B12 paves the way out to the following important regeneration by supporting the development of new cell structures. Furthermore, vitamin B1 facilitates the usage of carbohydrates for energy production, whereas vitamin B12 promotes nerve cell survival and remyelination. Absence of these vitamins will favor permanent nerve degeneration and pain, eventually leading to peripheral neuropathy.
Topics: Animals; Humans; Nerve Growth Factors; Nerve Regeneration; Vitamin B Complex
PubMed: 34337067
DOI: 10.1155/2021/9968228 -
The Lancet. Respiratory Medicine May 2021Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2... (Review)
Review
Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.
Topics: COVID-19; Cough; Humans; Inflammation; Nervous System Diseases; Neuroimmunomodulation; SARS-CoV-2; Syndrome
PubMed: 33857435
DOI: 10.1016/S2213-2600(21)00125-9 -
Microbiology (Reading, England) Sep 2020is a lethal fungus disguised in a polysaccharide coat. It can remain dormant in the host for decades prior to reactivation, causing systemic cryptococcosis in humans... (Review)
Review
is a lethal fungus disguised in a polysaccharide coat. It can remain dormant in the host for decades prior to reactivation, causing systemic cryptococcosis in humans and other mammals. deploys a multitude of traits to adapt to and survive within the host, including immunosuppression, an ability to replicate intra- and extra-cellularly in phagocytes, changes in morphology and ploidy, a predilection to infect the CNS, and the capacity to utilize neurotransmitters and unique carbon sources available in the brain. These pathogenic strategies displayed by this fungus might have evolved through its interactions with microbial predators in the environment.
Topics: Adaptation, Physiological; Animals; Cryptococcosis; Cryptococcus neoformans; Genome, Fungal; Humans; Phylogeny; Virulence
PubMed: 32956032
DOI: 10.1099/mic.0.000973 -
Handbook of Clinical Neurology 2014Viruses are important pathogens of the nervous system. Here we describe the basic properties of viruses and the principles of virus classification, evolution, structure,... (Review)
Review
Viruses are important pathogens of the nervous system. Here we describe the basic properties of viruses and the principles of virus classification, evolution, structure, and replication, with a focus on neurotropic viruses that are important neuropathogens of humans. These properties then provide the background for introductions to pathogenesis of viral diseases of the nervous system, host immune responses to virus infection, and the diagnosis and treatment of virus infections of the nervous system.
Topics: Animals; Humans; Virology; Viruses
PubMed: 25015480
DOI: 10.1016/B978-0-444-53488-0.00002-X -
Frontiers in Immunology 2021
Topics: Animals; Disease Susceptibility; Host-Parasite Interactions; Humans; Nerve Tissue; Organ Specificity; Parasites; Tropism
PubMed: 34659274
DOI: 10.3389/fimmu.2021.775666 -
Trends in Neurosciences May 2022Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection is associated with a diverse spectrum of neurological complications during the acute and postacute... (Review)
Review
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection is associated with a diverse spectrum of neurological complications during the acute and postacute stages. The pathogenesis of these complications is complex and dependent on many factors. For accurate and consistent interpretation of experimental data in this fast-growing field of research, it is essential to use terminology consistently. In this article, we outline the distinctions between neuroinvasiveness, neurotropism, and neurovirulence. Additionally, we discuss current knowledge of these distinct features underlying the pathogenesis of SARS-CoV-2-associated neurological complications. Lastly, we briefly discuss the advantages and limitations of different experimental models, and how these approaches can further be leveraged to advance the field.
Topics: COVID-19; Humans; Nervous System Diseases; SARS-CoV-2
PubMed: 35279295
DOI: 10.1016/j.tins.2022.02.006 -
Immunity Nov 2022While blood antibodies mediate protective immunity in most organs, whether they protect nasal surfaces in the upper airway is unclear. Using multiple viral infection...
While blood antibodies mediate protective immunity in most organs, whether they protect nasal surfaces in the upper airway is unclear. Using multiple viral infection models in mice, we found that blood-borne antibodies could not defend the olfactory epithelium. Despite high serum antibody titers, pathogens infected nasal turbinates, and neurotropic microbes invaded the brain. Using passive antibody transfers and parabiosis, we identified a restrictive blood-endothelial barrier that excluded circulating antibodies from the olfactory mucosa. Plasma cell depletions demonstrated that plasma cells must reside within olfactory tissue to achieve sterilizing immunity. Antibody blockade and genetically deficient models revealed that this local immunity required CD4 T cells and CXCR3. Many vaccine adjuvants failed to generate olfactory plasma cells, but mucosal immunizations established humoral protection of the olfactory surface. Our identification of a blood-olfactory barrier and the requirement for tissue-derived antibody has implications for vaccinology, respiratory and CNS pathogen transmission, and B cell fate decisions.
Topics: Animals; Mice; Plasma Cells; B-Lymphocytes; T-Lymphocytes; Immunoglobulins; Brain; Immunity, Mucosal; Antibodies, Viral
PubMed: 36137543
DOI: 10.1016/j.immuni.2022.08.017 -
Therapeutic Advances in Infectious... 2022The COVID-19 pandemic has shed light on the challenges we face as a global society in preventing and containing emerging and re-emerging pathogens. Multiple intersecting... (Review)
Review
The COVID-19 pandemic has shed light on the challenges we face as a global society in preventing and containing emerging and re-emerging pathogens. Multiple intersecting factors, including environmental changes, host immunological factors, and pathogen dynamics, are intimately connected to the emergence and re-emergence of communicable diseases. There is a large and expanding list of communicable diseases that can cause neurological damage, either through direct or indirect routes. Novel pathogens of neurotropic potential have been identified through advanced diagnostic techniques, including metagenomic next-generation sequencing, but there are also known pathogens which have expanded their geographic distribution to infect non-immune individuals. Factors including population growth, climate change, the increase in animal and human interface, and an increase in international travel and trade are contributing to the expansion of emerging and re-emerging pathogens. Challenges exist around antimicrobial misuse giving rise to antimicrobial-resistant infectious neurotropic organisms and increased susceptibility to infection related to the expanded use of immunomodulatory treatments. In this article, we will review key concepts around emerging and re-emerging pathogens and discuss factors associated with neurotropism and neuroinvasion. We highlight several neurotropic pathogens of interest, including West Nile virus (WNV), Zika Virus, Japanese Encephalitis Virus (JEV), and Tick-Borne Encephalitis Virus (TBEV). We emphasize neuroinfectious diseases which impact the central nervous system (CNS) and focus on flaviviruses, a group of vector-borne pathogens that have expanded globally in recent years and have proven capable of widespread outbreak.
PubMed: 35719177
DOI: 10.1177/20499361221102664 -
Viruses Jun 2021Astrovirus infections are among the main causes of diarrhea in children, but their significance for animal health has remained underestimated and largely unknown. This... (Review)
Review
Astrovirus infections are among the main causes of diarrhea in children, but their significance for animal health has remained underestimated and largely unknown. This is changing due to the increasing amount of newly identified neurotropic astroviruses in cases of nonsuppurative encephalitis and neurological disease in humans, pigs, ruminant species and minks. Neurological cases in ruminants and humans usually occur sporadically and as isolated cases. This contrasts with the situation in pigs and minks, in which diseases associated with neurotropic astroviruses are endemic and occur on the herd level. Affected animals show neurological signs such as mild ataxia to tetraplegia, loss of orientation or trembling, and the outcome is often fatal. Non-suppurative inflammation with perivascular cuffing, gliosis and neuronal necrosis are typical histological lesions of astrovirus encephalitis. Since astroviruses primarily target the gastrointestinal tract, it is assumed that they infect the brain through the circulatory system or retrograde following the nerves. The phylogenetic analysis of neurotropic astroviruses has revealed that they are genetically closely related, suggesting the presence of viral determinants for tissue tropism and neuroinvasion. In this review, we summarize the current knowledge on neurotropic astrovirus infections in animals and propose future research activities.
Topics: Animals; Astroviridae; Astroviridae Infections; Brain; Encephalitis, Viral; Genome, Viral; Nervous System Diseases; Phylogeny
PubMed: 34201545
DOI: 10.3390/v13071201 -
Cell Stem Cell Feb 2021ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters...
ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations.
Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; Apolipoproteins E; Astrocytes; Brain; COVID-19; Cell Differentiation; Chlorocebus aethiops; Humans; Induced Pluripotent Stem Cells; Nerve Degeneration; Neurites; Neurons; Organoids; Protein Isoforms; SARS-CoV-2; Synapses; Tropism; Vero Cells
PubMed: 33450186
DOI: 10.1016/j.stem.2020.12.018