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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial physiology: unique stimuli, specialized responses
Richard M Ransohoff1, V Hugh Perry
1Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. ransohr@ccf.org
Abstract:
Microglia, the macrophages of the central nervous system parenchyma, have in the normal healthy brain a distinct phenotype induced by molecules expressed on or secreted by adjacent neurons and astrocytes, and this phenotype is maintained in part by virtue of the blood-brain barrier's exclusion of serum components. Microglia are continually active, their processes palpating and surveying their local microenvironment. The microglia rapidly change their phenotype in response to any disturbance of nervous system homeostasis and are commonly referred to as activated on the basis of the changes in their morphology or expression of cell surface antigens. A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs. The term activated microglia needs to be qualified to reflect the distinct and very different states of activation-associated effector functions in different disease states. Manipulating the effector functions of microglia has the potential to modify the outcome of diverse neurological diseases.
Insights
Microglia, the brain's immune cells, constantly survey their environment. Their diverse functions and activation states in neurological diseases offer potential therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the central nervous system's resident macrophages.
- In a healthy brain, their phenotype is influenced by neural and glial cells and the blood-brain barrier.
- Microglia are constantly active, surveying their microenvironment.
Purpose of the Study:
- To describe the dynamic nature and diverse functions of microglia.
- To emphasize the need for qualifying the term "activated microglia" based on disease-specific states.
- To highlight the therapeutic potential of manipulating microglial functions in neurological diseases.
Main Methods:
- Review of existing literature on microglia biology and function.
- Analysis of microglial responses to disturbances in nervous system homeostasis.
- Examination of diverse effector functions in various disease contexts.
Main Results:
- Microglia exhibit a distinct phenotype in the healthy brain, maintained by local factors and the blood-brain barrier.
- Microglia rapidly alter their phenotype (morphology, antigen expression) in response to homeostatic disturbances, termed "activation".
- Microglia possess diverse effector functions, similar to macrophages in other organs, which vary significantly across different disease states.
Conclusions:
- The term "activated microglia" requires precise qualification to reflect distinct, disease-specific functional states.
- Understanding the diverse effector functions of microglia is crucial for developing targeted therapies.
- Modulating microglial effector functions holds significant potential for treating a wide range of neurological diseases.
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