A dynamic cellular response where microglia, the resident macrophages and primary immune surveillance cells of the central nervous system (CNS), transition from a quiescent, ramified state to an active, amoeboid phenotype. This activation is a fundamental component of the neuroinflammatory response to local injury, infection, or the presence of pathological protein aggregates. While essential for neuroprotection and debris clearance, chronic or excessive microglia activation contributes significantly to neuronal damage and the progression of neurodegenerative diseases.
Origin
The concept is rooted in neuroimmunology and cellular pathology, following the identification of microglia as the brain’s unique immune system in the early 20th century. The term describes the functional shift of these cells in response to a change in the brain’s microenvironment, known as the inflammatory cascade. Understanding the different activation states, such as pro-inflammatory (M1) and anti-inflammatory (M2), is a central focus of modern neuroscience.
Mechanism
Activation is typically triggered by the binding of pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) to specific pattern recognition receptors on the microglial surface. This binding initiates intracellular signaling pathways that lead to the transcription and release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. The resulting sustained neuroinflammation can disrupt the blood-brain barrier and significantly impair neuroendocrine and neuronal signaling pathways.
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