scholarly journals Activation and Regulation of Cellular Inflammasomes: Gaps in Our Knowledge for Central Nervous System Injury

2014 ◽  
Vol 34 (3) ◽  
pp. 369-375 ◽  
Author(s):  
Juan Pablo de Rivero Vaccari ◽  
W Dalton Dietrich ◽  
Robert W Keane
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Interleukin 1 ◽  
Cns Injury ◽  
Cord Injury ◽  
Cns Trauma ◽  
The Central Nervous System ◽  
Brain And Spinal Cord

The inflammasome is an intracellular multiprotein complex involved in the activation of caspase-1 and the processing of the proinflammatory cytokines interleukin-1 β (IL-1 β) and IL-18. The inflammasome in the central nervous system (CNS) is involved in the generation of an innate immune inflammatory response through IL-1 cytokine release and in cell death through the process of pyroptosis. In this review, we consider the different types of inflammasomes (NLRP1, NLRP2, NLRP3, and AIM2) that have been described in CNS cells, namely neurons, astrocytes, and microglia. Importantly, we focus on the role of the inflammasome after brain and spinal cord injury and cover the potential activators of the inflammasome after CNS injury such as adenosine triphosphate and DNA, and the therapeutic potential of targeting the inflammasome to improve outcomes after CNS trauma.

Effect of a central CRF antagonist on cardiovascular and thermoregulatory responses induced by stress or IL-1 beta

1993 ◽  
Vol 265 (4) ◽  
pp. R834-R839 ◽  
Author(s):  
T. Nakamori ◽  
A. Morimoto ◽  
N. Murakami
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Interleukin 1 ◽  
Corticotropin Releasing Factor ◽  
Mild Stress ◽  
Induced Responses ◽  
Interleukin 1 Beta ◽  
The Central Nervous System ◽  
Beta 2

We investigated the role of central corticotropin-releasing factor (CRF) in the development of cardiovascular and thermal responses induced by stress or by interleukin-1 beta (IL-1 beta) in free-moving rats. Intracerebroventricular (icv) injection of alpha-helical CRF9-41 (10 micrograms), a CRF receptor antagonist, significantly attenuated hypertension, tachycardia, and a rise in body temperature induced by cage-switch stress, a mild stress. However, icv injection of alpha-helical CRF9-41 (10 micrograms) had no effect on hypertension, tachycardia, or fever induced by intraperitoneal (ip) injection of IL-1 beta (2 micrograms/kg) or icv prostaglandin E2 (PGE2, 100 ng). In contrast, icv injection of alpha-helical CRF9-41 (10 micrograms) significantly attenuated hypertension, tachycardia, or fever induced by icv injection of IL-1 beta (20 ng). The present results suggest that central CRF has an important role in the development of the cage-switch stress-induced responses, but it does not seem to contribute to the hypertension, tachycardia, and fever induced by ip IL-1 beta or by central PGE2. However, it is possible that when IL-1 beta directly acts on the central nervous system, some of its actions are mediated by central CRF.

scholarly journals Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

2020 ◽  
Vol 21 (7) ◽  
pp. 2273
Author(s):  
Eunyoung Jung ◽  
Seong-Ho Koh ◽  
Myeongjong Yoo ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Carbon Monoxide ◽  
Nervous System ◽  
Neurotrophic Factors ◽  
Neural Circuits ◽  
Cns Injury ◽  
Cns Regeneration ◽  
The Central Nervous System ◽  
Endogenous Neural Stem Cells

Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS. The present review discusses the regenerative potential of CO in acute and chronic neuroinflammatory diseases of the CNS, such as stroke, traumatic brain injury, multiple sclerosis and Alzheimer’s disease and the role of signaling pathways and neurotrophic factors. CO-mediated facilitation of cellular communications may boost regeneration, consequently forming functional adult neural circuits in CNS injury.

scholarly journals Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ilse Bollaerts ◽  
Jessie Van houcke ◽  
Lien Andries ◽  
Lies De Groef ◽  
Lieve Moons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Current Knowledge ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
The Impact ◽  
Vertebrate Central Nervous System

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies.

Role of the glucose-dependent insulinotropic polypeptide and its receptor in the central nervous system: therapeutic potential in neurological diseases

2010 ◽  
Vol 21 (5-6) ◽  
pp. 394-408 ◽  
Author(s):  
Cláudia P. Figueiredo ◽  
Fabrício A. Pamplona ◽  
Tânia L. Mazzuco ◽  
Aderbal S. Aguiar ◽  
Roger Walz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
The Central Nervous System

scholarly journals Impact of Gabapentin and Pregabalin on Neurological Outcome After Central Nervous System Injury

2020 ◽  
Vol 3 ◽  
Author(s):  
Caleb Morton ◽  
Fen-Lei Cheng
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retrospective Chart Review ◽  
Potential Method ◽  
Cns Injury ◽  
Cell Dysfunction ◽  
Significant Difference ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Short And Long Term

Background and Purpose:   Injury to the central nervous system (CNS) is often detrimental to the health, functionality, and quality of life in both the short- and long-term. Injuries that fall under this umbrella include traumatic brain injury (TBI), traumatic spinal cord injury (TSCI), and stroke. These types of injuries vary in what initiates them, but their proposed mechanisms leading to cell dysfunction and death are strikingly similar. There has been pre-clinical and limited retrospective data supporting the idea that gabapentin and pregabalin both have neuroprotective qualities and may alleviate some of the sub-acute damage initiated by these different injuries. The purpose of this study is to determine whether patients taking either gabapentin or pregabalin at the time of their injury tend to have better outcomes than patients with similar injuries who were not taking either one of the two medications.  Methods:  This is a retrospective chart review analysis of 600 patients admitted to Parkview Hospitals from 2016-2019 for TBI, TSCI, or stroke. The outcomes of patients taking either gabapentin or pregabalin with one of the prior diagnoses will be compared to patients with the same diagnosis who were not taking either of the medications mentioned. Statistical analysis will be performed to evaluate if any significant difference exists between the outcomes at discharge of patients taking either medication versus patients who were not.  Results:  Results will be listed as comparisons between patients grouped by injury, and sub-grouped by medication usage. P-values will be included to show significance of comparisons.  Conclusion and Potential Impact:   The main impact of this study is to provide evidence and support leading to a potential method to improve outcomes in patients with CNS injuries. Secondary impacts are providing basis for development of a CNS injury registry and support for developing a unified CNS injury assessment scale to allow comparison of the treatments of different 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 Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2353
Author(s):  
Maja Potokar ◽  
Jernej Jorgačevski
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Proteins ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Plectin, a high-molecular-mass cytolinker, is abundantly expressed in the central nervous system (CNS). Currently, a limited amount of data about plectin in the CNS prevents us from seeing the complete picture of how plectin affects the functioning of the CNS as a whole. Yet, by analogy to its role in other tissues, it is anticipated that, in the CNS, plectin also functions as the key cytoskeleton interlinking molecule. Thus, it is likely involved in signalling processes, thereby affecting numerous fundamental functions in the brain and spinal cord. Versatile direct and indirect interactions of plectin with cytoskeletal filaments and enzymes in the cells of the CNS in normal physiological and in pathologic conditions remain to be fully addressed. Several pathologies of the CNS related to plectin have been discovered in patients with plectinopathies. However, in view of plectin as an integrator of a cohesive mesh of cellular proteins, it is important that the role of plectin is also considered in other CNS pathologies. This review summarizes the current knowledge of plectin in the CNS, focusing on plectin isoforms that have been detected in the CNS, along with its expression profile and distribution alongside diverse cytoskeleton filaments in CNS cell types. Considering that the bidirectional communication between neurons and glial cells, especially astrocytes, is crucial for proper functioning of the CNS, we place particular emphasis on the known roles of plectin in neurons, and we propose possible roles of plectin in astrocytes.

scholarly journals Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system

2003 ◽  
Vol 162 (2) ◽  
pp. 233-243 ◽  
Author(s):  
Catherine I. Dubreuil ◽  
Matthew J. Winton ◽  
Lisa McKerracher
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axon Growth ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Cord Injury ◽  
The Central Nervous System

Growth inhibitory proteins in the central nervous system (CNS) block axon growth and regeneration by signaling to Rho, an intracellular GTPase. It is not known how CNS trauma affects the expression and activation of RhoA. Here we detect GTP-bound RhoA in spinal cord homogenates and report that spinal cord injury (SCI) in both rats and mice activates RhoA over 10-fold in the absence of changes in RhoA expression. In situ Rho-GTP detection revealed that both neurons and glial cells showed Rho activation at SCI lesion sites. Application of a Rho antagonist (C3–05) reversed Rho activation and reduced the number of TUNEL-labeled cells by ∼50% in both injured mouse and rat, showing a role for activated Rho in cell death after CNS injury. Next, we examined the role of the p75 neurotrophin receptor (p75NTR) in Rho signaling. After SCI, an up-regulation of p75NTR was detected by Western blot and observed in both neurons and glia. Treatment with C3–05 blocked the increase in p75NTR expression. Experiments with p75NTR-null mutant mice showed that immediate Rho activation after SCI is p75NTR dependent. Our results indicate that blocking overactivation of Rho after SCI protects cells from p75NTR-dependent apoptosis.

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.

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