Molecular mechanisms in CNS injury – The importance of therapeutic modification of cytokine expression in the brains of domestic animals

2004 ◽  
Vol 168 (3) ◽  
pp. 205-206 ◽  
Author(s):  
Marc Vandevelde
Keyword(s):  
Molecular Mechanisms ◽  
Domestic Animals ◽  
Cytokine Expression ◽  
Cns Injury

scholarly journals Tracing the origins of SARS-COV-2 in coronavirus phylogenies: a review

2021 ◽  
Vol 19 (2) ◽  
pp. 769-785 ◽  
Author(s):  
Erwan Sallard ◽  
José Halloy ◽  
Didier Casane ◽  
Etienne Decroly ◽  
Jacques van Helden
Keyword(s):  
Sequence Analysis ◽  
Structure Function ◽  
Molecular Mechanisms ◽  
Laboratory Strain ◽  
Domestic Animals ◽  
Scientific Policy ◽  
Human Coronavirus ◽  
Viral Dissemination ◽  
Link Type ◽  
Intensive Breeding

AbstractSARS-CoV-2 is a new human coronavirus (CoV), which emerged in China in late 2019 and is responsible for the global COVID-19 pandemic that caused more than 97 million infections and 2 million deaths in 12 months. Understanding the origin of this virus is an important issue, and it is necessary to determine the mechanisms of viral dissemination in order to contain future epidemics. Based on phylogenetic inferences, sequence analysis and structure–function relationships of coronavirus proteins, informed by the knowledge currently available on the virus, we discuss the different scenarios on the origin—natural or synthetic—of the virus. The data currently available are not sufficient to firmly assert whether SARS-CoV2 results from a zoonotic emergence or from an accidental escape of a laboratory strain. This question needs to be solved because it has important consequences on the risk/benefit balance of our interactions with ecosystems, on intensive breeding of wild and domestic animals, on some laboratory practices and on scientific policy and biosafety regulations. Regardless of COVID-19 origin, studying the evolution of the molecular mechanisms involved in the emergence of pandemic viruses is essential to develop therapeutic and vaccine strategies and to prevent future zoonoses. This article is a translation and update of a French article published in Médecine/Sciences, August/September 2020 (10.1051/medsci/2020123).

scholarly journals Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury

2015 ◽  
Vol 112 (43) ◽  
pp. 13360-13365 ◽  
Author(s):  
Hongmei Duan ◽  
Weihong Ge ◽  
Aifeng Zhang ◽  
Yue Xi ◽  
Zhihua Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Cns Injury ◽  
Neurotrophin 3 ◽  
Cord Injury ◽  
Transcriptome Analyses ◽  
Regeneration Capability

Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.

scholarly journals Deletion or Inhibition of Astrocytic Transglutaminase 2 Promotes Functional Recovery after Spinal Cord Injury

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2942
Author(s):  
Anissa Elahi ◽  
Jacen Emerson ◽  
Jacob Rudlong ◽  
Jeffrey W. Keillor ◽  
Garrick Salois ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Functional Recovery ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Transglutaminase 2 ◽  
Cns Injury ◽  
Post Injury ◽  
Metabolic Coupling ◽  
Cord Injury ◽  
Spinal Cord Contusion

Following CNS injury, astrocytes become “reactive” and exhibit pro-regenerative or harmful properties. However, the molecular mechanisms that cause astrocytes to adopt either phenotype are not well understood. Transglutaminase 2 (TG2) plays a key role in regulating the response of astrocytes to insults. Here, we used mice in which TG2 was specifically deleted in astrocytes (Gfap-Cre+/− TG2fl/fl, referred to here as TG2-A-cKO) in a spinal cord contusion injury (SCI) model. Deletion of TG2 from astrocytes resulted in a significant improvement in motor function following SCI. GFAP and NG2 immunoreactivity, as well as number of SOX9 positive cells, were significantly reduced in TG2-A-cKO mice. RNA-seq analysis of spinal cords from TG2-A-cKO and control mice 3 days post-injury identified thirty-seven differentially expressed genes, all of which were increased in TG2-A-cKO mice. Pathway analysis revealed a prevalence for fatty acid metabolism, lipid storage and energy pathways, which play essential roles in neuron–astrocyte metabolic coupling. Excitingly, treatment of wild type mice with the selective TG2 inhibitor VA4 significantly improved functional recovery after SCI, similar to what was observed using the genetic model. These findings indicate the use of TG2 inhibitors as a novel strategy for the treatment of SCI and other CNS injuries.

scholarly journals The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 121 ◽  
Author(s):  
Yonghee Kim ◽  
Jinhong Park ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Bk Channel ◽  
Cns Injury ◽  
Antioxidant Agents ◽  
The Central Nervous System

Astrocytes outnumber neurons in the human brain, and they play a key role in numerous functions within the central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) and water homeostasis, defense against oxidative/nitrosative stress, energy storage, mitochondria biogenesis, scar formation, tissue repair via angiogenesis and neurogenesis, and synapse modulation. After CNS injury, astrocytes communicate with surrounding neuronal and vascular systems, leading to the clearance of disease-specific protein aggregates, such as β-amyloid, and α-synuclein. The astrocytic big conductance K+ (BK) channel plays a role in these processes. Recently, potential therapeutic agents that target astrocytes have been tested for their potential to repair the brain. In this review, we discuss the role of the BK channel and antioxidant agents such as heme oxygenase metabolites following CNS injury. A better understanding of the cellular and molecular mechanisms of astrocytes’ functions in the healthy and diseased brains will greatly contribute to the development of therapeutic approaches following CNS injury, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

scholarly journals Molecular Mechanisms of Central Nervous System Axonal Regeneration and Remyelination: A Review

2020 ◽  
Vol 21 (21) ◽  
pp. 8116
Author(s):  
Akiko Uyeda ◽  
Rieko Muramatsu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Motor Deficits ◽  
Cns Injury ◽  
Cellular Mechanisms ◽  
Cns Regeneration ◽  
Cord Injury ◽  
Extracellular Environment ◽  
Injury Causes

Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor deficits. Currently, there is no effective therapeutic method to restore neurological function because the adult CNS has limited capacity to regenerate after injury. Many efforts have been made to understand the molecular and cellular mechanisms underlying CNS regeneration and to establish novel therapeutic methods based on these mechanisms, with a variety of strategies including cell transplantation, modulation of cell intrinsic molecular mechanisms, and therapeutic targeting of the pathological nature of the extracellular environment in CNS injury. In this review, we will focus on the mechanisms that regulate CNS regeneration, highlighting the history, recent efforts, and questions left unanswered in this field.

REVIEW ■ : Calcium and the Pathogenesis of Traumatic CNS Injury: Cellular and Molecular Mechanisms

1997 ◽  
Vol 3 (3) ◽  
pp. 169-175 ◽  
Author(s):  
Tracy K. Mcintosh ◽  
Kathryn E. Saatman ◽  
Ramesh Raghupathi
Keyword(s):  
Molecular Mechanisms ◽  
Cns Injury

scholarly journals Pathological Neuroinflammatory Conversion of Reactive Astrocytes Is Induced by Microglia and Involves Chromatin Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Alejandro Villarreal ◽  
Camila Vidos ◽  
Matías Monteverde Busso ◽  
María Belén Cieri ◽  
Alberto Javier Ramos
Keyword(s):  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Reactive Astrocytes ◽  
Pharmacological Intervention ◽  
Temporary Increase ◽  
Epigenetic Changes ◽  
Cns Injury ◽  
Gain Of Function ◽  
Pathological Remodeling

Following brain injury or in neurodegenerative diseases, astrocytes become reactive and may suffer pathological remodeling, features of which are the loss of their homeostatic functions and a pro-inflammatory gain of function that facilitates neurodegeneration. Pharmacological intervention to modulate this astroglial response and neuroinflammation is an interesting new therapeutic research strategy, but it still requires a deeper understanding of the underlying cellular and molecular mechanisms of the phenomenon. Based on the known microglial–astroglial interaction, the prominent role of the nuclear factor kappa B (NF-κB) pathway in mediating astroglial pathological pro-inflammatory gain of function, and its ability to recruit chromatin-remodeling enzymes, we first explored the microglial role in the initiation of astroglial pro-inflammatory conversion and then monitored the progression of epigenetic changes in the astrocytic chromatin. Different configurations of primary glial culture were used to modulate microglia–astrocyte crosstalk while inducing pro-inflammatory gain of function by lipopolysaccharide (LPS) exposure. In vivo, brain ischemia by cortical devascularization (pial disruption) was performed to verify the presence of epigenetic marks in reactive astrocytes. Our results showed that 1) microglia is required to initiate the pathological conversion of astrocytes by triggering the NF-κB signaling pathway; 2) this interaction is mediated by soluble factors and induces stable astroglial phenotypic changes; 3) the pathological conversion promotes chromatin remodeling with stable increase in H3K9K14ac, temporary increase in H3K27ac, and temporary reduction in heterochromatin mark H3K9me3; and 4) in vivo reactive astrocytes show increased H3K27ac mark in the neuroinflammatory milieu from the ischemic penumbra. Our findings indicate that astroglial pathological pro-inflammatory gain of function is associated with profound changes in the configuration of astrocytic chromatin, which in turn are initiated by microglia-derived cues. These results open a new avenue in the study of potential pharmacological interventions that modify the initiation and stabilization of astroglial pathological remodeling, which would be useful in acute and chronic CNS injury. Epigenetic changes represent a plausible pharmacological target to interfere with the stabilization of the pathological astroglial phenotype.

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