Microglia Activation During Neuroinflammation: Overview

Click on one of the stages of microglia activation to see the molecules involved in that process.

Healthy Neuron
Healthy Neuron

Maintenance of
"Resting" Microglia

Maintenance of
"Resting" Microglia

Microglia
Steady-State
Markers

Microglia
Steady-State
Markers

Ramified Microglia
Ramified Microglia
Insult
Insult
Injured Neuron
Injured Neuron
Lytic Enzymes
Lytic Enzymes
Extracellular Matrix
(ECM)
Extracellular Matrix
(ECM)
Neural
Injury-Derived
DAMPs
Neural
Injury-Derived
DAMPs
ECM-Derived
DAMPs
ECM-Derived
DAMPs

Microglia
Activation

Microglia
Activation

Neurodegenerative
Disease-Related
DAMPs
Neurodegenerative
Disease-Related
DAMPs
Astrocyte
Astrocyte
Th1 Cell
Th1 Cell
Th2 Cell
Th2 Cell

Microglia
Polarization

Microglia
Polarization

M1 Phenotype
M1 Phenotype
M2 Phenotype
M2 Phenotype
Onset
Onset
Time After Insult
Time After Insult
TNF-alpha
IFN-gamma
GM-CSF
IL-1 beta/IL-1F2
IL-6
TNF-alpha
IFN-gamma
GM-CSF
IL-1 beta/IL-1F2
IL-6
IL-4
IL-13
IL-4
IL-13
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Neuroinflammation, defined as inflammation of nervous tissue, is initiated in response to a variety of endogenous and exogenous sources including invading pathogens, neuronal injury, and toxic compounds. It is characterized by glial cell activation, the release of inflammatory molecules, increased blood-brain barrier permeability, and recruitment of peripheral immune cells into the brain. Neuroinflammation is initiated by microglia, which are the resident immune cells of the central nervous system. Under steady-state conditions, microglia are maintained in a “resting” state through interactions with cell surface and soluble factors from surrounding cells. Microglia become activated following exposure to pathogen-associated molecular patterns (PAMPs) and/or endogenous damage-associated molecular patterns (DAMPs), and removal of the immune-suppressive signals. Activated microglia can acquire different phenotypes depending on cues in its surrounding environment. M1 microglia are initially present following an insult as they promote a proinflammatory response. Over time, the response is shifted to be anti-inflammatory, which is mediated by M2 microglia. In truth, current research has suggested that microglia activation is more complex than originally believed. It has been suggested that there is a range of microglia activation states that span from the M1 to M2 phenotypes, with each phenotype displaying different markers, secreting different compounds, and exhibiting different functions.

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Microglia Activation During Neuroinflammation: Overview  background image 1