scholarly journals Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

2021 ◽  
Vol 15 ◽  
Author(s):  
GuiLian Yu ◽  
Ying Zhang ◽  
Bin Ning
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Phenotypic Diversity ◽  
Expression Profiles ◽  
Reactive Astrocytes ◽  
Cns Injury ◽  
Cord Injury

Traumatic central nervous system (CNS) injury, which includes both traumatic brain injury (TBI) and spinal cord injury (SCI), is associated with irreversible loss of neurological function and high medical care costs. Currently, no effective treatment exists to improve the prognosis of patients. Astrocytes comprise the largest population of glial cells in the CNS and, with the advancements in the field of neurology, are increasingly recognized as having key functions in both the brain and the spinal cord. When stimulated by disease or injury, astrocytes become activated and undergo a series of changes, including alterations in gene expression, hypertrophy, the loss of inherent functions, and the acquisition of new ones. Studies have shown that astrocytes are highly heterogeneous with respect to their gene expression profiles, and this heterogeneity accounts for their observed context-dependent phenotypic diversity. In the inured CNS, activated astrocytes play a dual role both as regulators of neuroinflammation and in scar formation. Identifying the subpopulations of reactive astrocytes that exert beneficial or harmful effects will aid in deciphering the pathological mechanisms underlying CNS injuries and ultimately provide a theoretical basis for the development of effective strategies for the treatment of associated conditions. Following CNS injury, as the disease progresses, astrocyte phenotypes undergo continuous changes. Although current research methods do not allow a comprehensive and accurate classification of astrocyte subpopulations in complex pathological contexts, they can nonetheless aid in understanding the roles of astrocytes in disease. In this review, after a brief introduction to the pathology of CNS injury, we summarize current knowledge regarding astrocyte activation following CNS injury, including: (a) the regulatory factors involved in this process; (b) the functions of different astrocyte subgroups based on the existing classification of astrocytes; and (c) attempts at astrocyte-targeted therapy.

scholarly journals Identification of clinical and radiographic predictors of central nervous system injury in genetic skeletal disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antônio L Cunha ◽  
Ana P S Champs ◽  
Carla M. Mello ◽  
Mônica M. M. Navarro ◽  
Frederico J. C. Godinho ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Low Back Pain ◽  
Back Pain ◽  
Low Back ◽  
Cns Injury ◽  
Cord Injury ◽  
Skeletal Disorders

AbstractSome studies report neurological lesions in patients with genetic skeletal disorders (GSDs). However, none of them describe the frequency of neurological lesions in a large sample of patients or investigate the associations between clinical and/or radiological central nervous system (CNS) injury and clinical, anthropometric and imaging parameters. The project was approved by the institution’s ethics committee (CAAE 49433215.5.0000.0022). In this cross-sectional observational analysis study, 272 patients aged four or more years with clinically and radiologically confirmed GSDs were prospectively included. Genetic testing confirmed the diagnosis in the FGFR3 chondrodysplasias group. All patients underwent blinded and independent clinical, anthropometric and neuroaxis imaging evaluations. Information on the presence of headache, neuropsychomotor development (NPMD), low back pain, joint deformity, ligament laxity and lower limb discrepancy was collected. Imaging abnormalities of the axial skeleton and CNS were investigated by whole spine digital radiography, craniocervical junction CT and brain and spine MRI. The diagnostic criteria for CNS injury were abnormal clinical and/or radiographic examination of the CNS. Brain injury included malacia, encephalopathies and malformation. Spinal cord injury included malacia, hydrosyringomyelia and spinal cord injury without radiographic abnormalities. CNS injury was diagnosed in more than 25% of GSD patients. Spinal cord injury was found in 21.7% of patients, and brain injury was found in 5.9%. The presence of low back pain, os odontoideum and abnormal NPMD remained independently associated with CNS injury in the multivariable analysis. Early identification of these abnormalities may have some role in preventing compressive CNS injury, which is a priority in GSD patients.

scholarly journals Role of NETosis in Central Nervous System Injury

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Yituo Chen ◽  
Haojie Zhang ◽  
Xinli Hu ◽  
Wanta Cai ◽  
Wenfei Ni ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Nervous System ◽  
Brain Injury ◽  
Cns Injury ◽  
Cell Death Pathways ◽  
Cord Injury

Central nervous system (CNS) injury is divided into brain injury and spinal cord injury and remains the most common cause of morbidity and mortality worldwide. Previous reviews have defined numerous inflammatory cells involved in this process. In the human body, neutrophils comprise the largest numbers of myeloid leukocytes. Activated neutrophils release extracellular web-like DNA amended with antimicrobial proteins called neutrophil extracellular traps (NETs). The formation of NETs was demonstrated as a new method of cell death called NETosis. As the first line of defence against injury, neutrophils mediate a variety of adverse reactions in the early stage, and we consider that NETs may be the prominent mediators of CNS injury. Therefore, exploring the specific role of NETs in CNS injury may help us shed some light on early changes in the disease. Simultaneously, we discovered that there is a link between NETosis and other cell death pathways by browsing other research, which is helpful for us to establish crossroads between known cell death pathways. Currently, there is a large amount of research concerning NETosis in various diseases, but the role of NETosis in CNS injury remains unknown. Therefore, this review will introduce the role of NETosis in CNS injury, including traumatic brain injury, cerebral ischaemia, CNS infection, Alzheimer’s disease, and spinal cord injury, by describing the mechanism of NETosis, the evidence of NETosis in CNS injury, and the link between NETosis and other cell death pathways. Furthermore, we also discuss some agents that inhibit NETosis as therapies to alleviate the severity of CNS injury. NETosis may be a potential target for the treatment of CNS injury, so exploring NETosis provides a feasible therapeutic option for CNS injury in the future.

Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

1982 ◽  
Vol 60 (11) ◽  
pp. 1415-1424 ◽  
Author(s):  
H. B. Demopoulos ◽  
E. S. Flamm ◽  
M. L. Seligman ◽  
D. D. Pietronigro ◽  
J. Tomasula ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Free Radical ◽  
Tissue Injury ◽  
Functional Restoration ◽  
Radical Reactions ◽  
Free Radical Reactions ◽  
Cord Injury

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.

scholarly journals Beyond the lesion site: minocycline augments inflammation and anxiety-like behavior following SCI in rats through action on the gut microbiota

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Emma K. A. Schmidt ◽  
Pamela J. F. Raposo ◽  
Abel Torres-Espin ◽  
Keith K. Fenrich ◽  
Karim Fouad
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Gut Microbiota ◽  
Microglial Activation ◽  
Motor Recovery ◽  
Long Term Effects ◽  
Cord Injury ◽  
Anti Inflammatory

Abstract Background Minocycline is a clinically available synthetic tetracycline derivative with anti-inflammatory and antibiotic properties. The majority of studies show that minocycline can reduce tissue damage and improve functional recovery following central nervous system injuries, mainly attributed to the drug’s direct anti-inflammatory, anti-oxidative, and neuroprotective properties. Surprisingly the consequences of minocycline’s antibiotic (i.e., antibacterial) effects on the gut microbiota and systemic immune response after spinal cord injury have largely been ignored despite their links to changes in mental health and immune suppression. Methods Here, we sought to determine minocycline’s effect on spinal cord injury-induced changes in the microbiota-immune axis using a cervical contusion injury in female Lewis rats. We investigated a group that received minocycline following spinal cord injury (immediately after injury for 7 days), an untreated spinal cord injury group, an untreated uninjured group, and an uninjured group that received minocycline. Plasma levels of cytokines/chemokines and fecal microbiota composition (using 16s rRNA sequencing) were monitored for 4 weeks following spinal cord injury as measures of the microbiota-immune axis. Additionally, motor recovery and anxiety-like behavior were assessed throughout the study, and microglial activation was analyzed immediately rostral to, caudal to, and at the lesion epicenter. Results We found that minocycline had a profound acute effect on the microbiota diversity and composition, which was paralleled by the subsequent normalization of spinal cord injury-induced suppression of cytokines/chemokines. Importantly, gut dysbiosis following spinal cord injury has been linked to the development of anxiety-like behavior, which was also decreased by minocycline. Furthermore, although minocycline attenuated spinal cord injury-induced microglial activation, it did not affect the lesion size or promote measurable motor recovery. Conclusion We show that minocycline’s microbiota effects precede its long-term effects on systemic cytokines and chemokines following spinal cord injury. These results provide an exciting new target of minocycline as a therapeutic for central nervous system diseases and injuries.

scholarly journals Single-cell immune repertoire and transcriptome sequencing reveals that clonally expanded and transcriptionally distinct lymphocytes populate the aged central nervous system in mice

2021 ◽  
Vol 288 (1945) ◽  
pp. 20202793
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cells ◽  
Single Cell ◽  
Somatic Hypermutation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
The Central Nervous System

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.

scholarly journals Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury

RSC Advances ◽  
2020 ◽  
Vol 10 (32) ◽  
pp. 18677-18686
Author(s):  
Jia Liu ◽  
Kai Li ◽  
Ke Huang ◽  
Chengliang Yang ◽  
Zhipeng Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Traumatic Injury ◽  
High Rate ◽  
Plga Microspheres ◽  
Cord Injury ◽  
The Central Nervous System

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery.

Central Nervous System Reorganization and Pain After Spinal Cord Injury: Possible Targets for Physical Therapy—A Systematic Review of Neuroimaging Studies

2020 ◽  
Vol 100 (6) ◽  
pp. 946-962
Author(s):  
Thomas Osinski ◽  
Sessi Acapo ◽  
Djamel Bensmail ◽  
Didier Bouhassira ◽  
Valéria Martinez
Keyword(s):  
Systematic Review ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Physical Therapist ◽  
Anterior Cingulate ◽  
Current Evidence ◽  
Functional Changes ◽  
Cord Injury

Abstract Background Pain is one of the main symptoms associated with spinal cord injury (SCI) and can be associated with changes to the central nervous system (CNS). Purpose This article provides an overview of the evidence relating to CNS changes (structural and functional) associated with pain in SCIs. Data Sources A systematic review was performed, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, on PubMed, Embase, and Web of Science in March 2018. Study Selection Studies were selected if they concerned changes in the CNS of patients with SCI, regardless of the type of imagery. Data Extraction Data were extracted by 2 blinded reviewers. Data Synthesis There is moderate evidence for impaired electroencephalographic function and metabolic abnormalities in the anterior cingulate in patients experiencing pain. There is preliminary evidence that patients with pain have morphological and functional changes to the somatosensory cortex and alterations to thalamic metabolism. There are conflicting data regarding the relationships between lesion characteristics and pain. In contrast, patients without pain can display protective neuroplasticity. Limitations and Conclusion Further studies are required to elucidate fully the relationships between pain and neuroplasticity in patients with SCIs. However, current evidence might support the use of physical therapist treatments targeting CNS plasticity in patients with SCI pain.

Sign in / Sign up

Export Citation Format

Share Document