ArticleBrain : a journal of neurology2017
Inhibition of the P2X7-PANX1 complex suppresses spreading depolarization and neuroinflammation.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of the causes and consequences of spreading depolarization in neuroinflammation; implications for neurovascular disorders.Journal of neuroinflammation · 2025Pooled it
- Altered Pannexin2 Expression in Retinal Degeneration: Insights from the P23H Mouse Model of Retinis Pigmentosa.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- P2X7 Receptor in Rare Diseases: Shared Molecular Mechanisms and Therapeutic Implications.Journal of inflammation research · 2026Review
- Spreading depolarization in neurocritical care: a review of SD'S pathophysiological continuum and clinical translation.Frontiers in human neuroscience · 2026Review
- Spreading depolarization as a therapeutic target in migraine.Nature reviews. Neurology · 2025Review
- The relationship between lung function and headache risk in middle-aged and older adults: a cross-sectional and longitudinal study.European journal of medical research · 2025Article
- Spreading depolarization triggers pro- and anti-inflammatory signalling: a potential link to headache.Brain : a journal of neurology · 2025Article
- Activation of central and peripheral transient receptor potential melastatin 8 increases susceptibility to spreading depolarization and facilitates trigeminal neuroinflammation.The journal of headache and pain · 2025Article
- The link between spreading depolarization and innate immunity in the central nervous system.The journal of headache and pain · 2025Review
- Pharmacological inhibition of all known major inward cationic currents does not block the induction of spreading depolarizations.Frontiers in cellular neuroscience · 2025Article
- Low-intensity pulsed ultrasound ameliorates partial infraorbital nerve ligation-induced trigeminal neuropathic pain through inhibiting Schwann cell Pannexin 1 channel.Frontiers in immunology · 2025Article
- Unraveling the interplay of neuroinflammatory signaling between parenchymal and meningeal cells in migraine headache.The journal of headache and pain · 2024Review
- The effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation.The journal of headache and pain · 2024Article
- Role of HDAC5 Epigenetics in Chronic Craniofacial Neuropathic Pain.International journal of molecular sciences · 2024Review
- Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression.Biological research · 2024Article
- Constitutive and evoked release of ATP in adult mouse olfactory epithelium.Open life sciences · 2024Article
- Migraine Duration as a Potential Amplifier of Obesity.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- Vesicular HMGB1 release from neurons stressed with spreading depolarization enables confined inflammatory signaling to astrocytes.Journal of neuroinflammation · 2023Article
- Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache.Molecular and cellular biochemistry · 2023Review
- Advanced brain MRI may help understand the link between migraine and multiple sclerosis.The journal of headache and pain · 2023Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation. We found that genetic loss of function or ablation of the P2x7 gene inhibits spreading depolarization. Moreover, pharmacological suppression of the P2X7-PANX1 pore complex inhibits spreading depolarization in mice carrying the human familial hemiplegic migraine type 1 R192Q missense mutation as well as in wild-type mice and rats. Pore inhibitors elevate the electrical threshold for spreading depolarization, and reduce spreading depolarization frequency and amplitude. Pore inhibitors also suppress downstream consequences of spreading depolarization such as upregulation of interleukin-1 beta, inducible nitric oxide synthase and cyclooxygenase-2 in the cortex after spreading depolarization. In addition, they inhibit surrogates for trigeminovascular activation, including expression of calcitonin gene-related peptide in the trigeminal ganglion and c-Fos in the trigeminal nucleus caudalis. Our results are consistent with the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility and its downstream consequences, of potential relevance to its signature disorders such as migraine.
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