ArticleThe journal of headache and pain2021
Src family kinases activity is required for transmitting purinergic P2X7 receptor signaling in cortical spreading depression and neuroinflammation.
Article in The journal of headache and pain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- A systematic review of the causes and consequences of spreading depolarization in neuroinflammation; implications for neurovascular disorders.Journal of neuroinflammation · 2025Pooled it
- Review
- Focusing on inflammation-driven pyroptosis in postherpetic neuralgia: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- Targeting SAA expression via siRNA mitigates preterm birth induced by maternal inflammation.Frontiers in pharmacology · 2026Article
- The link between spreading depolarization and innate immunity in the central nervous system.The journal of headache and pain · 2025Review
- [Targets and Molecular Mechanisms of Salidroside in Improving High-Altitude Cognitive Function].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Structure of Full-Length Src Kinase and Its Key Phosphorylated States: Molecular Dynamics Study.International journal of molecular sciences · 2024Article
- Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity.The journal of headache and pain · 2024Article
- Nano-selenium and the SRC family kinases pathway: Redefining gene expression dynamics in major depressive disorder based on a randomized controlled trial.Current journal of neurology · 2024Article
- Unraveling the interplay of neuroinflammatory signaling between parenchymal and meningeal cells in migraine headache.The journal of headache and pain · 2024Review
- Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties.Cell & bioscience · 2023Review
- Experimental and Clinical Investigation of Cytokines in Migraine: A Narrative Review.International journal of molecular sciences · 2023Review
- Transcranial Magnetic Stimulation as a Therapy for Migraine: An Overview of Systematic Reviews.Journal of pain research · 2023Article
- Article
- P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine.The journal of headache and pain · 2022Article
- Astrocytic Glutamatergic Transmission and Its Implications in Neurodegenerative Disorders.Cells · 2022Review
- Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundPurinergic P2X7 receptor plays an important role in migraine pathophysiology. Yet precise molecular mechanism underlying P2X7R signaling in migraine remains unclear. This study explores the hypothesis that P2X7 receptor transmits signaling to Src family kinases (SFKs) during cortical spreading depression (CSD) and neuroinflammation after CSD.
methodsCSD was recorded using electrophysiology in rats and intrinsic optical imaging in mouse brain slices. Cortical IL-1β and TNFα mRNA levels were detected using qPCR. Glutamate release from mouse brain slices was detected using glutamate assay.
resultsThe data showed that deactivation of SFKs by systemic injection of PP2 reduced cortical susceptibility to CSD in rats and CSD-induced IL-1β and TNF-α gene expression in rat ipsilateral cortices. Consistently, in mouse brain slices, inhibition of SFKs activity by saracatinib and P2X7 receptor by A740003 similarly reduced cortical susceptibility to CSD. When the interaction of P2X7 receptor and SFKs was disrupted by TAT-P2X7, a marked reduction of cortical susceptibility to CSD, IL-1β gene expression and glutamate release after CSD induction were observed in mouse brain slices. The reduced cortical susceptibility to CSD by TAT-P2X7 was restored by NMDA, and disrupting the Fyn-NMDA interaction using TAT-Fyn (39-57) but not disrupting Src-NMDA receptor interaction using TAT-Src (40-49) reduced cortical susceptibility to CSD. Furthermore, activation of P2X7 receptor by BzATP restored the TAT-Fyn (39-57)-reduced cortical susceptibility to CSD.
conclusionThis study reveals that SFKs activity transmits P2X7 receptor signaling to facilitate CSD propagation via glutamatergic pathway and promote neuroinflammation, which is of particular relevance to migraine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.