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The Journal of Headache and Pain

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Open Access 01-12-2022 | Migraine | Research article

FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats

Authors: Yanjie Zhou, Lily Zhang, Yuyan Hao, Liu Yang, Shanghua Fan, Zheman Xiao

Published in: The Journal of Headache and Pain | Issue 1/2022

Abstract

Background

The incidence of migraines is higher among individuals with epilepsy than in healthy individuals, and these two diseases are thought to shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglial activation is crucial for abnormal neuronal signal transmission. However, it remains unclear whether and how microglia are activated and their role in comorbidities after being activated. This study aimed to explore the characteristics and mechanism of microglial activation after seizures and their effect on migraine.

Methods

Model rats of status epilepticus (SE) induced by intraperitoneal injection of lithium chloride (LiCl)-pilocarpine and migraine induced by repeated dural injections of inflammatory soup (IS) were generated, and molecular and histopathologic evidence of the microglial activation targets of fractalkine (FKN) signalling were examined. HT22-BV2 transwell coculture assays were used to explore the interaction between neurons and microglia. LPS (a microglial agonist) and FKN stimulation of BV2 microglial cells were used to evaluate changes in BDNF levels after microglial activation.

Results

Microglia were specifically hyperplastic and activated in the temporal lobe cortex, thalamus, and spinal trigeminal nucleus caudalis (sp5c), accompanied by the upregulation of FKN and CX3CR1 four days after seizures. Moreover, SE-induced increases in nociceptive behaviour and FKN/CX3CR1 axis expression in migraine model rats. AZD8797 (a CX3CR1 inhibitor) prevented the worsening of hyperalgesia and microglial activation in migraine model rats after seizures, while FKN infusion in migraine model rats exacerbated hyperalgesia and microglial activation associated with BDNF-Trkb signalling. Furthermore, in neuron-microglia cocultures, microglial activation and FKN/CX3CR1/BDNF/iba1 expression were increased compared with those in microglial cultures alone. Activating microglia with LPS and FKN increased BDNF synthesis in BV2 microglia.

Conclusions

Our results indicated that epilepsy facilitated migraine through FKN/CX3CR1 axis-mediated microglial activation in the cortex/thalamus/sp5c, which was accompanied by BDNF release. Blocking the FKN/CX3CR1 axis and microglial activation are potential therapeutic strategies for preventing and treating migraine in patients with epilepsy.

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Yanjie Zhou, Lily Zhang, Yuyan Hao et al. FKN/CX3CR1 Axis Facilitated Migraine-like Behaviors via Activating Thalamic-cortical Network Microglia in SE Rat Models. PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1085216/v1].

Title: FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats
Authors: Yanjie Zhou
Lily Zhang
Yuyan Hao
Liu Yang
Shanghua Fan
Zheman Xiao
Publication date: 01-12-2022
Publisher: Springer Milan
Keywords: Migraine
Status Epilepticus
Epilepsy
Epileptic Seizure
Published in: The Journal of Headache and Pain / Issue 1/2022
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-022-01416-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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