scholarly journals SARS-CoV-2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

2020 ◽  
Author(s):  
Veronica Murta ◽  
Alejandro Villarreal ◽  
Alberto Javier Ramos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Experimental Models ◽  
Circumventricular Organs ◽  
Target Cells ◽  
Neurological Manifestations ◽  
Cns Inflammation ◽  
The Central Nervous System

With confirmed COVID-19 cases surpassing the 8.5 million mark around the globe, there is an imperative need to deepen the efforts from the international scientific community to gain comprehensive understanding of SARS-CoV-2. Although the main clinical manifestations are associated with respiratory or intestinal symptoms, reports of specific and non-specific neurological signs and symptoms, both at presentation or during the course of the acute phase, are increasing. Approximately 25-40% of the patients present neurological symptoms. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the Central Nervous System (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier (BBB). Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for MERS-CoV. Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to dysbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this work we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV, explore the potential role for astrocytes and microglia in the infection and neuroinflammation, and compare them with the previously described human and animal CoV that showed neurotropism. We also propose possible underlying mechanisms by focusing on our knowledge of glia, neurons, and their dynamic intricate communication with the immune system.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

ASN NEURO ◽  
2020 ◽  
Vol 12 ◽  
pp. 175909142095496 ◽  
Author(s):  
Veronica Murta ◽  
Alejandro Villarreal ◽  
Alberto J. Ramos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Manifestations ◽  
Experimental Models ◽  
Circumventricular Organs ◽  
Target Cells ◽  
Neurological Manifestations ◽  
Cns Inflammation ◽  
The Central Nervous System

With confirmed coronavirus disease 2019 (COVID-19) cases surpassing the 18 million mark around the globe, there is an imperative need to gain comprehensive understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are associated with respiratory or intestinal symptoms, reports of neurological signs and symptoms are increasing. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the central nervous system (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood–brain barrier. Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS rennin-angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for Middle East respiratory syndrome coronavirus (MERS-CoV). Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes, and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to disbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this comprehensive review, we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV; explore the potential role for astrocytes and microglia in the infection and neuroinflammation; and compare them with the previously described human and animal CoV that showed neurotropism to propose possible underlying mechanisms.

scholarly journals Signs and Symptoms of Central Nervous System Involvement and Their Pathogenesis in COVID-19 According to The Clinical Data (Review)

2021 ◽  
Vol 17 (3) ◽  
pp. 65-77
Author(s):  
N. V. Tsygan ◽  
A. P. Trashkov ◽  
A. V. Ryabtsev ◽  
V. A. Yakovleva ◽  
A. L. Konevega ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Data ◽  
Nervous Tissue ◽  
Central Nervous System Involvement ◽  
Signs And Symptoms ◽  
Neurological Manifestations ◽  
Altered Level ◽  
System Involvement ◽  
The Central Nervous System

Detailed clinical assessment of the central nervous system involvement in SARS-CoV-2 infection is relevant due to the low specificity of neurological manifestations, the complexity of evaluation of patient complaints, reduced awareness of the existing spectrum of neurological manifestations of COVID-19, as well as low yield of the neurological imaging.The aim. To reveal the patterns of central nervous system involvement in COVID-19 and its pathogenesis based on clinical data.Among more than 200 primary literature sources from various databases (Scopus, Web of Science, RSCI, etc.), 80 sources were selected for evaluation, of them 72 were published in the recent years (2016-2020). The criteria for exclusion of sources were low relevance and outdated information.The clinical manifestations of central nervous system involvement in COVID-19 include smell (5-98% of cases) and taste disorders (6-89%), dysphonia (28%), dysphagia (19%), consciousness disorders (3-53%), headache (0-70%), dizziness (0-20%), and, in less than 3% of cases, visual impairment, hearing impairment, ataxia, seizures, stroke. Analysis of the literature data revealed the following significant mechanisms of the effects of highly contagious coronaviruses (including SARS-CoV-2) on the central nervous system: neurodegeneration (including cytokine- induced); cerebral thrombosis and thromboembolism; damage to the neurovascular unit; immune-mediated damage of nervous tissue, resulting in infection and allergy-induced demyelination.The neurological signs and symptoms seen in COVID-19 such as headache, dizziness, impaired smell and taste, altered level of consciousness, bulbar disorders (dysphagia, dysphonia) have been examined. Accordingly, we discussed the possible routes of SARS-CoV-2 entry into the central nervous system and the mechanisms of nervous tissue damage.Based on the literature analysis, a high frequency and variability of central nervous system manifestations of COVID-19 were revealed, and an important role of vascular brain damage and neurodegeneration in the pathogenesis of COVID-19 was highlighted.

Clinical manifestations of antiphospholipid syndrome associated with lesions of the central nervous system

2016 ◽  
Vol 94 (5) ◽  
pp. 391-394
Author(s):  
A. V. Budnevskiy ◽  
V. A. Kutashov ◽  
Andrey Ya. Kravchenko
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Antiphospholipid Syndrome ◽  
Clinical Case ◽  
Clinical Manifestations ◽  
Neurological Manifestations ◽  
Cerebral Blood Vessels ◽  
Cerebrovascular Accidents ◽  
The Central Nervous System

Antiphospholipid syndrome (APS) is one of the important but poorly known conditions. Its symptoms are ofparticular interest for neurologists since thrombi are most often localized in the cerebral blood vessels which leads to ischemic cerebrovascular accidents (AICS). APS can also manifest itself in the following symptoms: epileptic attacks, dementia, headache, chorea, peripheral neuropathy, myelo- and encephalopathy phenomenologically similar to multiple sclerosis. This article presents a clinical case of secondary APS with the neurological manifestations in a 25-year-old female patient.

scholarly journals Delivery of Therapeutic Agents to the Central Nervous System and the Promise of Extracellular Vesicles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 492
Author(s):  
Charlotte A. René ◽  
Robin J. Parks
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Significant Barrier ◽  
The Central Nervous System ◽  
Delivery Vehicles

The central nervous system (CNS) is surrounded by the blood–brain barrier (BBB), a semipermeable border of endothelial cells that prevents pathogens, solutes and most molecules from non-selectively crossing into the CNS. Thus, the BBB acts to protect the CNS from potentially deleterious insults. Unfortunately, the BBB also frequently presents a significant barrier to therapies, impeding passage of drugs and biologicals to target cells within the CNS. This review provides an overview of different approaches to deliver therapeutics across the BBB, with an emphasis in extracellular vesicles as delivery vehicles to the CNS.

scholarly journals Biology of the repair of central nervous system demyelinated lesions: an appraisal

1996 ◽  
Vol 54 (2) ◽  
pp. 331-334 ◽  
Author(s):  
L. A. V Peireira ◽  
M. A. Cruz-Höfling ◽  
M. S. J. Dertkigil ◽  
D. L. Graça
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Schwann Cells ◽  
Demyelinating Disease ◽  
Experimental Models ◽  
Primitive Cell ◽  
Marked Influence ◽  
Myelin Sheaths ◽  
Human Material ◽  
The Central Nervous System

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.

scholarly journals Infection of the central nervous system with dengue virus 3 genotype I causing neurological manifestations in Brazil

2016 ◽  
Vol 49 (1) ◽  
pp. 125-129 ◽  
Author(s):  
Danilo Bretas de Oliveira ◽  
Guilherme Machado ◽  
Gabriel Magno de Freitas Almeida ◽  
Paulo César Peregrino Ferreira ◽  
Cláudio Antônio Bonjardim ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Dengue Virus ◽  
Neurological Manifestations ◽  
Genotype I ◽  
The Central Nervous System

scholarly journals Neurons Are Host Cells for Mycobacterium tuberculosis

2014 ◽  
Vol 82 (5) ◽  
pp. 1880-1890 ◽  
Author(s):  
Philippa J. Randall ◽  
Nai-Jen Hsu ◽  
Dirk Lang ◽  
Susan Cooper ◽  
Boipelo Sebesho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mycobacterium Tuberculosis ◽  
Host Cells ◽  
Productive Infection ◽  
Target Cells ◽  
Dependent Manner ◽  
Content Type ◽  
The Central Nervous System

ABSTRACTMycobacterium tuberculosisinfection of the central nervous system is thought to be initiated once the bacilli have breached the blood brain barrier and are phagocytosed, primarily by microglial cells. In this study, the interactions ofM. tuberculosiswith neuronsin vitroandin vivowere investigated. The data obtained demonstrate that neurons can act as host cells forM. tuberculosis.M. tuberculosisbacilli were internalized by murine neuronal cultured cells in a time-dependent manner after exposure, with superior uptake by HT22 cells compared to Neuro-2a cells (17.7% versus 9.8%). Internalization ofM. tuberculosisbacilli by human SK-N-SH cultured neurons suggested the clinical relevance of the findings. Moreover, primary murine hippocampus-derived neuronal cultures could similarly internalizeM. tuberculosis. InternalizedM. tuberculosisbacilli represented a productive infection with retention of bacterial viability and replicative potential, increasing 2- to 4-fold within 48 h.M. tuberculosisbacillus infection of neurons was confirmedin vivoin the brains of C57BL/6 mice after intracerebral challenge. This study, therefore, demonstrates neurons as potential new target cells forM. tuberculosiswithin the central nervous system.

scholarly journals Autonomous requirements of the Menkes disease protein in the nervous system

2015 ◽  
Vol 309 (10) ◽  
pp. C660-C668 ◽  
Author(s):  
Victoria L. Hodgkinson ◽  
Sha Zhu ◽  
Yanfang Wang ◽  
Erik Ladomersky ◽  
Karen Nickelson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Copper Deficiency ◽  
Copper Homeostasis ◽  
Signs And Symptoms ◽  
Menkes Disease ◽  
Copper Transporter ◽  
Sensorimotor Deficits ◽  
The Central Nervous System

Menkes disease is a fatal neurodegenerative disorder arising from a systemic copper deficiency caused by loss-of-function mutations in a ubiquitously expressed copper transporter, ATP7A. Although this disorder reveals an essential role for copper in the developing human nervous system, the role of ATP7A in the pathogenesis of signs and symptoms in affected patients, including severe mental retardation, ataxia, and excitotoxic seizures, remains unknown. To directly examine the role of ATP7A within the central nervous system, we generated Atp7a Nes mice, in which the Atp7a gene was specifically deleted within neural and glial cell precursors without impairing systemic copper homeostasis, and compared these mice with the mottled brindle ( mo-br) mutant, a murine model of Menkes disease in which Atp7a is defective in all cells. Whereas mo-br mice displayed neurodegeneration, demyelination, and 100% mortality prior to weaning, the Atp7a Nes mice showed none of these phenotypes, exhibiting only mild sensorimotor deficits, increased anxiety, and susceptibility to NMDA-induced seizure. Our results indicate that the pathophysiology of severe neurological signs and symptoms in Menkes disease is the result of copper deficiency within the central nervous system secondary to impaired systemic copper homeostasis and does not arise from an intrinsic lack of ATP7A within the developing brain. Furthermore, the sensorimotor deficits, hypophagia, anxiety, and sensitivity to NMDA-induced seizure in the Atp7a Nes mice reveal unique autonomous requirements for ATP7A in the nervous system. Taken together, these data reveal essential roles for copper acquisition in the central nervous system in early development and suggest novel therapeutic approaches in affected patients.

scholarly journals Postoperative agitation syndrome in young children with perinatal damage to the central nervous system

2021 ◽  
Vol 16 (5) ◽  
pp. 355-360
Author(s):  
V.I. Snisar ◽  
O.S. Pavlysh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Young Children ◽  
Postoperative Period ◽  
Anesthetic Management ◽  
Clinical Manifestations ◽  
Postoperative Recovery ◽  
Inhalation Anesthesia ◽  
Ventriculoperitoneal Shunting ◽  
The Central Nervous System

One of the complications of the postoperative period in children is postanesthetic agitation, a significant emotional and uncontrollable worry, clouding of consciousness, feeling of anxiety and fear, inappropriate behavior, irritability, inconso­lable crying, aggressive and negative attitude towards parents and medical staff. Postoperative agitation is very important for clinicians and hospitals, it has a risk of harming a patient, staying longer in the ward after anesthesia, and increasing the period of postoperative recovery. The frequency of postoperative agitation depends on age group. Most often agitation occurs in young children. There is evidence that agitation can also be due to the immature nervous system and a consequence of pathological conditions of the central nervous system (asthenoneurotic syndrome, encephalopathy, hyperactivity syndrome, perinatal posthypoxic and organic brain lesions, history of prematurity, epilepsy, psychophysical and speech delay, etc.). That is why the goal of our research was to study the patterns of clinical manifestations of postoperative agitation syndrome in children with prenatal da­mage to the central nervous system. The work was performed based on the analysis of the postoperative period in 109 young children: 59 patients with acquired hydrocephalus, who underwent ventriculoperitoneal shunting, and 50 children without neurological disorders in whom reconstructive surge­ries were carried out. Depending on the type anesthetic management, each group was divided into two subgroups: children, who received inhalation anesthesia with sevoflurane, and those, who received total intravenous anesthesia using propofol. In the postoperative period, the behavior of children was assessed on a Pediatric Ane­sthesia Emergence Delirium scale 30 minutes after anesthesia was completed. Criterion for the development of agitation was the presence of excitement in a child with a score of ≥ 10 points. Study showed that young children with perinatal damage to the central nervous system and children whose anesthetic provision is carried out using sevoflurane are the most vulnerable to the development of agitation syndrome. Agitation in such children is more pronounced and longer. These cases require prediction, detection and active surveillance.

scholarly journals Autoantibodies Against Ubiquitous and Confined Antigens in Patients With Ocular, Neuro-Ophthalmic and Congenital Cerebral Toxoplasmosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Monica Goldberg-Murow ◽  
Carlos Cedillo-Peláez ◽  
Luz Elena Concha-del-Río ◽  
Rashel Cheja-Kalb ◽  
María José Salgar-Henao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mimicry ◽  
Clinical Manifestations ◽  
Protective Role ◽  
Cross Reactivity ◽  
Ocular Toxoplasmosis ◽  
Cerebral Toxoplasmosis ◽  
Blood Retinal Barrier ◽  
The Central Nervous System

Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).

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