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Updated: Jul 27, 2025
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
The status of knowledge on migraines: The role of microglia
Wei He1, Yanyun Wang2, Yixin Zhang2
1Department of Neurology, The First Branch of The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
Migraines are a considerable social problem and economic burden worldwide. Current acute treatments are based on inhibiting meningeal neurogenic inflammation which has poor results in some patients, whereas the site of action of prophylactic medicines are unknown; therefore, exploring new treatment mechanisms and methods is increasingly needed. Recent evidence suggests that microglia and microglia-mediated neuroinflammation are important in migraine pathogenesis. In the cortical spreading depression (CSD) migraine model, microglia were activated after multiple CSD stimulations, suggesting that microglial activation may be associated with recurrent attacks of migraine with aura. In the nitroglycerin-induced chronic migraine model, the microglial response to extracellular stimuli leads to the activation of surface purine receptors P2X4、P2X7、P2Y12, which mediate signal transduction through intracellular signalling cascades, such as the BDNF/TrkB, NLRP3/IL-1β and RhoA/ROCK signalling pathways, and release inflammatory mediators and cytokines that enhance pain by increasing the excitability of nearby neurons. Inhibition of the expression or function of these microglial receptors and pathways inhibits the abnormal excitability of TNC (trigeminal nucleus caudalis) neurons and intracranial as well as extracranial hyperalgesia in migraine animal models. These findings suggest that microglia may be central in migraine recurrent attacks and a potential target for the treatment of chronic headaches.
Insights
Microglia and neuroinflammation play a key role in migraine pathogenesis. Targeting microglial purine receptors and signaling pathways offers a promising new strategy for treating chronic headaches and migraines.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Migraine is a significant global health issue with limited treatment efficacy.
- Current migraine treatments targeting neuroinflammation show variable results.
- The precise mechanisms underlying migraine pathogenesis, especially chronic forms, require further elucidation.
Purpose of the Study:
- To investigate the role of microglia and microglial-mediated neuroinflammation in migraine pathogenesis.
- To explore novel therapeutic targets for migraine treatment by examining microglial activation pathways.
Main Methods:
- Utilized animal models of migraine, including cortical spreading depression (CSD) and nitroglycerin-induced chronic migraine.
- Examined microglial activation in response to CSD and chronic migraine stimuli.
- Investigated the involvement of purine receptors (P2X4, P2X7, P2Y12) and intracellular signaling cascades (BDNF/TrkB, NLRP3/IL-1β, RhoA/ROCK) in microglia.
- Assessed the effects of inhibiting microglial receptors and pathways on neuronal excitability and hyperalgesia in animal models.
Main Results:
- Microglial activation was observed in response to CSD and in a chronic migraine model.
- Activation of microglial purine receptors (P2X4, P2X7, P2Y12) triggers inflammatory signaling pathways.
- These pathways lead to the release of inflammatory mediators that increase neuronal excitability and pain.
- Inhibition of these microglial targets reduced trigeminal nucleus caudalis (TNC) neuron hyperexcitability and hyperalgesia in migraine models.
Conclusions:
- Microglia are centrally involved in the recurrent attacks of migraine.
- Microglial purine receptors and associated signaling pathways represent potential therapeutic targets for migraine and chronic headache treatment.
