The brain is a complex network system that has the capacity to support emotion, thought, action, learning and memory, and is characterized by constant activity, constant structural remodeling, and constant attempt to ...The brain is a complex network system that has the capacity to support emotion, thought, action, learning and memory, and is characterized by constant activity, constant structural remodeling, and constant attempt to compensate for this remodeling. The basic insight that emerges from complex network organization is that substantively different networks can share common key organizational principles. Moreover, the interdependence of network organization and behavior has been successfully demonstrated for several specific tasks. From this viewpoint, increasing experimental/clinical observations suggest that mental disorders are neural network disorders. On one hand, single psychiatric disorders arise from multiple, multifactorial molecular and cellular structural/functional alterations spreading throughout local/global circuits leading to multifaceted and heterogeneous clinical symptoms. On the other hand, various mental diseases may share functional deficits across the same neural circuit as reflected in the overlap of symptoms throughout clinical diagnoses. An integrated framework including experimental measures and clinical observations will be necessary to formulate a coherent and comprehensive understanding of how neural connectivity mediates and constraints the phenotypic expression of psychiatric disorders.展开更多
Axon growth is a central event in the development and post-injury plasticity of the nervous system. Growing axons encounter a wide variety of environmental instructions. Much like traffic lights in controlling the mig...Axon growth is a central event in the development and post-injury plasticity of the nervous system. Growing axons encounter a wide variety of environmental instructions. Much like traffic lights in controlling the migrating axons, chondroitin sulfate proteoglycans (CSPGs) and heparan sulfate proteoglycans (HSPGs) often lead to "stop" and "go" growth responses in the axons, respectively. Recently, the LAR family and NgR family molecules were identified as neuronal receptors for CSPGs and HSPGs. These discoveries provided molecular tools for further study of mechanisms underlying axon growth regulation. More importantly, the identification of these proteoglycan receptors offered potential therapeutic targets for promoting post-injury axon regeneration.展开更多
Glucocorticoid and glucocorticoid receptor(GC/GR) interactions alter numerous aspects of neuronal function. These consequences(e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC...Glucocorticoid and glucocorticoid receptor(GC/GR) interactions alter numerous aspects of neuronal function. These consequences(e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC exposure or central nervous system(CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing.展开更多
Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient on and axon poten...Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient on and axon potential propagation. In the normal adult CNS, the extracellular matrix (ECM) is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/ central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed.展开更多
文摘The brain is a complex network system that has the capacity to support emotion, thought, action, learning and memory, and is characterized by constant activity, constant structural remodeling, and constant attempt to compensate for this remodeling. The basic insight that emerges from complex network organization is that substantively different networks can share common key organizational principles. Moreover, the interdependence of network organization and behavior has been successfully demonstrated for several specific tasks. From this viewpoint, increasing experimental/clinical observations suggest that mental disorders are neural network disorders. On one hand, single psychiatric disorders arise from multiple, multifactorial molecular and cellular structural/functional alterations spreading throughout local/global circuits leading to multifaceted and heterogeneous clinical symptoms. On the other hand, various mental diseases may share functional deficits across the same neural circuit as reflected in the overlap of symptoms throughout clinical diagnoses. An integrated framework including experimental measures and clinical observations will be necessary to formulate a coherent and comprehensive understanding of how neural connectivity mediates and constraints the phenotypic expression of psychiatric disorders.
文摘Axon growth is a central event in the development and post-injury plasticity of the nervous system. Growing axons encounter a wide variety of environmental instructions. Much like traffic lights in controlling the migrating axons, chondroitin sulfate proteoglycans (CSPGs) and heparan sulfate proteoglycans (HSPGs) often lead to "stop" and "go" growth responses in the axons, respectively. Recently, the LAR family and NgR family molecules were identified as neuronal receptors for CSPGs and HSPGs. These discoveries provided molecular tools for further study of mechanisms underlying axon growth regulation. More importantly, the identification of these proteoglycan receptors offered potential therapeutic targets for promoting post-injury axon regeneration.
文摘Glucocorticoid and glucocorticoid receptor(GC/GR) interactions alter numerous aspects of neuronal function. These consequences(e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC exposure or central nervous system(CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing.
基金supported by NIH/NINDS R01-NS043246,P30-NS045758,the International Spinal Research Trust(STR-100)the Ohio State University College of Medicine
文摘Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient on and axon potential propagation. In the normal adult CNS, the extracellular matrix (ECM) is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/ central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed.