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1.
Diabetes Metab Syndr ; 15(6): 102305, 2021.
Article in English | MEDLINE | ID: covidwho-1506436

ABSTRACT

Covid-19 associated several neurological manifestation in the form of Post-infectious transverse myelitis(TM) and para-infectious TM has been reported. A 54 years old female patient presented to us with acute retention of urine and upper motor neuron type of bilateral lower limb weakness in shock stage, after 12 days of covid-19 infection. MRI (3T) brain and spine showed no abnormality and Nerve conduction study showed acquired motor axonal polyradiculoneuropathy in bilateral lower limbs. We herein present an index case of MRI-negative myeloradiculoneuropathy following covid-19 infection.


Subject(s)
COVID-19/complications , Central Nervous System Diseases/pathology , Magnetic Resonance Imaging/methods , Motor Neuron Disease/pathology , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Central Nervous System Diseases/etiology , Female , Humans , Middle Aged , Motor Neuron Disease/etiology
2.
Acta Neuropathol ; 142(6): 923-936, 2021 12.
Article in English | MEDLINE | ID: covidwho-1459953

ABSTRACT

As extremely sensitive immune cells, microglia act as versatile watchdogs of the central nervous system (CNS) that tightly control tissue homeostasis. Therefore, microglial activation is an early and easily detectable hallmark of virtually all neuropsychiatric, neuro-oncological, neurodevelopmental, neurodegenerative and neuroinflammatory diseases. The recent introduction of novel high-throughput technologies and several single-cell methodologies as well as advances in epigenetic analyses helped to identify new microglia expression profiles, enhancer-landscapes and local signaling cues that defined diverse previously unappreciated microglia states in the healthy and diseased CNS. Here, we give an overview on the recent developments in the field of microglia biology and provide a practical guide to analyze disease-associated microglia phenotypes in both the murine and human CNS, on several morphological and molecular levels. Finally, technical limitations, potential pitfalls and data misinterpretations are discussed as well.


Subject(s)
Microglia , Animals , Central Nervous System Diseases/pathology , Humans , Mice , Neuropathology , Phenotype
3.
Brain Res Bull ; 177: 155-163, 2021 12.
Article in English | MEDLINE | ID: covidwho-1433004

ABSTRACT

The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its threat to humans have drawn worldwide attention. The acute and long-term effects of SARS-CoV-2 on the nervous system pose major public health challenges. Patients with SARS-CoV-2 present diverse symptoms of the central nervous system. Exploring the mechanism of coronavirus damage to the nervous system is essential for reducing the long-term neurological complications of COVID-19. Despite rapid progress in characterizing SARS-CoV-2, the long-term effects of COVID-19 on the brain remain unclear. The possible mechanisms of SARS-CoV-2 injury to the central nervous system include: 1) direct injury of nerve cells, 2) activation of the immune system and inflammatory cytokines caused by systemic infection, 3) a high affinity of the SARS-CoV-2 spike glycoprotein for the angiotensin-converting enzyme ACE2, 4) cerebrovascular disease caused by hypoxia and coagulation dysfunction, and 5) a systemic inflammatory response that promotes cognitive impairment and neurodegenerative diseases. Although we do not fully understand the mechanism by which SARS-CoV-2 causes nerve injury, we hope to provide a framework by reviewing the clinical manifestations, complications, and possible mechanisms of neurological damage caused by SARS-CoV-2. With hope, this will facilitate the early identification, diagnosis, and treatment of possible neurological sequelae, which could contribute toward improving patient prognosis and preventing transmission.


Subject(s)
COVID-19/complications , Central Nervous System Diseases/virology , Central Nervous System Diseases/pathology , Humans , SARS-CoV-2
4.
Int J Mol Sci ; 22(3)2021 Jan 26.
Article in English | MEDLINE | ID: covidwho-1389389

ABSTRACT

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients' CNS and serve as a platform for therapeutic development and personalized precision medicine.


Subject(s)
Central Nervous System Diseases/drug therapy , Drug Discovery/methods , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Tissue Engineering/methods , Animals , COVID-19/drug therapy , COVID-19/pathology , Central Nervous System Diseases/pathology , Drug Discovery/instrumentation , Drug Evaluation, Preclinical/instrumentation , Drug Evaluation, Preclinical/methods , Humans , Induced Pluripotent Stem Cells/pathology , Lab-On-A-Chip Devices , Organoids/cytology , Organoids/drug effects , Organoids/pathology , Tissue Engineering/instrumentation , Zika Virus Infection/drug therapy , Zika Virus Infection/pathology
5.
Neurochem Int ; 148: 105101, 2021 09.
Article in English | MEDLINE | ID: covidwho-1271730

ABSTRACT

Central nervous system (CNS) diseases are responsible for a large proportion of morbidity and mortality worldwide. CNS diseases caused by intrinsic and extrinsic stimuli stimulate the resident immune cells including microglia and astrocyte, resulting in neuroinflammation that exacerbates the progression of diseases. Recent evidence reveals the aberrant expression patterns of long non-coding RNAs (lncRNAs) in the damaged tissues following CNS diseases. It was also proposed that lncRNAs possessed immune-modulatory activities by directly or indirectly affecting various effector proteins including transcriptional factor, acetylase, protein kinase, phosphatase, etc. In addition, lncRNAs can form a sophisticated network by interacting with other molecules to regulate the expression or activation of downstream immune response pathways. However, the major roles of lncRNAs in CNS pathophysiologies are still elusive, especially in neuroinflammation. Herein, we tend to review some potential roles of lncRNAs in modulating neuroinflammation based on current evidence in various CNS diseases, in order to provide novel explanations for the initiation and progression of CNS diseases and help to establish therapeutic strategies targeting neuroinflammation.


Subject(s)
Central Nervous System Diseases/genetics , RNA, Long Noncoding/physiology , Animals , Central Nervous System Diseases/drug therapy , Central Nervous System Diseases/pathology , Humans , /pathology , RNA, Long Noncoding/genetics
6.
J Comput Assist Tomogr ; 45(4): 592-599, 2021.
Article in English | MEDLINE | ID: covidwho-1284963

ABSTRACT

OBJECTIVE: The aim of the study was to aggregate neuroradiological findings in patients with coronavirus disease 2019 (COVID-19) in the brain, head and neck, and spine to identify trends and unique patterns. METHODS: A retrospective review of neuroimaged COVID-19 patients during a 6-week surge in our 8-hospital campus was performed. The brain imaging with reported acute or subacute infarction, intraparenchymal hemorrhage, and all neck examinations were reinterpreted by 2 reviewers. RESULTS: Six hundred seventy-one patients met criteria and were reviewed. Acute or subacute infarction was seen in 39 (6%), intraparenchymal hemorrhage in 14 (2%), corpus callosum involvement in 7, and thalamus in 5 patients. In spine and neck studies, lung opacities and adenopathy were seen in 46 and 4 patients, respectively. CONCLUSIONS: Infarction followed by intraparenchymal hemorrhage was the most common acute findings in the brain with frequent involvement of the corpus callosum and thalami. In the neck, lung abnormalities were frequently present, and adenopathy was almost always associated with a second pathology.


Subject(s)
COVID-19/complications , COVID-19/pathology , Central Nervous System Diseases/complications , Central Nervous System Diseases/diagnostic imaging , Neuroimaging/methods , Adolescent , Adult , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain/pathology , COVID-19/diagnostic imaging , Central Nervous System Diseases/pathology , Child , Child, Preschool , Female , Head/diagnostic imaging , Head/pathology , Humans , Infant , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neck/diagnostic imaging , Neck/pathology , Pandemics , Retrospective Studies , SARS-CoV-2 , Spine/diagnostic imaging , Spine/pathology , Tomography, X-Ray Computed/methods , Young Adult
7.
Brief Bioinform ; 22(5)2021 09 02.
Article in English | MEDLINE | ID: covidwho-1174876

ABSTRACT

Current coronavirus disease-2019 (COVID-19) pandemic has caused massive loss of lives. Clinical trials of vaccines and drugs are currently being conducted around the world; however, till now no effective drug is available for COVID-19. Identification of key genes and perturbed pathways in COVID-19 may uncover potential drug targets and biomarkers. We aimed to identify key gene modules and hub targets involved in COVID-19. We have analyzed SARS-CoV-2 infected peripheral blood mononuclear cell (PBMC) transcriptomic data through gene coexpression analysis. We identified 1520 and 1733 differentially expressed genes (DEGs) from the GSE152418 and CRA002390 PBMC datasets, respectively (FDR < 0.05). We found four key gene modules and hub gene signature based on module membership (MMhub) statistics and protein-protein interaction (PPI) networks (PPIhub). Functional annotation by enrichment analysis of the genes of these modules demonstrated immune and inflammatory response biological processes enriched by the DEGs. The pathway analysis revealed the hub genes were enriched with the IL-17 signaling pathway, cytokine-cytokine receptor interaction pathways. Then, we demonstrated the classification performance of hub genes (PLK1, AURKB, AURKA, CDK1, CDC20, KIF11, CCNB1, KIF2C, DTL and CDC6) with accuracy >0.90 suggesting the biomarker potential of the hub genes. The regulatory network analysis showed transcription factors and microRNAs that target these hub genes. Finally, drug-gene interactions analysis suggests amsacrine, BRD-K68548958, naproxol, palbociclib and teniposide as the top-scored repurposed drugs. The identified biomarkers and pathways might be therapeutic targets to the COVID-19.


Subject(s)
Brain Neoplasms/pathology , Central Nervous System Diseases/pathology , Computational Biology/methods , Glioblastoma/pathology , Machine Learning , Algorithms , Disease Progression , Humans
8.
Int J Mol Sci ; 22(3)2021 Jan 26.
Article in English | MEDLINE | ID: covidwho-1050617

ABSTRACT

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients' CNS and serve as a platform for therapeutic development and personalized precision medicine.


Subject(s)
Central Nervous System Diseases/drug therapy , Drug Discovery/methods , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Tissue Engineering/methods , Animals , COVID-19/drug therapy , COVID-19/pathology , Central Nervous System Diseases/pathology , Drug Discovery/instrumentation , Drug Evaluation, Preclinical/instrumentation , Drug Evaluation, Preclinical/methods , Humans , Induced Pluripotent Stem Cells/pathology , Lab-On-A-Chip Devices , Organoids/cytology , Organoids/drug effects , Organoids/pathology , Tissue Engineering/instrumentation , Zika Virus Infection/drug therapy , Zika Virus Infection/pathology
9.
Mol Neurobiol ; 58(2): 520-535, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-797979

ABSTRACT

The main discussion above of the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has focused substantially on the immediate risks and impact on the respiratory system; however, the effects induced to the central nervous system are currently unknown. Some authors have suggested that SARS-CoV-2 infection can dramatically affect brain function and exacerbate neurodegenerative diseases in patients, but the mechanisms have not been entirely described. In this review, we gather information from past and actual studies on coronaviruses that informed neurological dysfunction and brain damage. Then, we analyzed and described the possible mechanisms causative of brain injury after SARS-CoV-2 infection. We proposed that potential routes of SARS-CoV-2 neuro-invasion are determinant factors in the process. We considered that the hematogenous route of infection can directly affect the brain microvascular endothelium cells that integrate the blood-brain barrier and be fundamental in initiation of brain damage. Additionally, activation of the inflammatory response against the infection represents a critical step on injury induction of the brain tissue. Consequently, the virus' ability to infect brain cells and induce the inflammatory response can promote or increase the risk to acquire central nervous system diseases. Here, we contribute to the understanding of the neurological conditions found in patients with SARS-CoV-2 infection and its association with the blood-brain barrier integrity.


Subject(s)
Blood-Brain Barrier/virology , Brain/virology , COVID-19/complications , Central Nervous System Diseases/virology , Inflammation/virology , Blood-Brain Barrier/pathology , Brain/pathology , COVID-19/pathology , Central Nervous System Diseases/pathology , Humans , Inflammation/pathology
10.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165889, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-627951

ABSTRACT

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.


Subject(s)
Central Nervous System Diseases/pathology , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Animals , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Central Nervous System Diseases/complications , Central Nervous System Diseases/virology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Humans , Lung/metabolism , Lung/virology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Envelope Proteins/antagonists & inhibitors , Viral Envelope Proteins/metabolism , Viral Fusion Proteins/antagonists & inhibitors , Viral Fusion Proteins/metabolism , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolism
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