ArticleBrain : a journal of neurology2013
Antagonism of purinergic signalling improves recovery from traumatic brain injury.
Article in Brain : a journal of neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 88 citations in OpenAlex.
- Gasotransmitters in the regulation of connexins in central and peripheral nervous system injuries.Medical gas research · 2027Review
- Calcium Signaling in Astrocytes and Its Role in the Central Nervous System Injury.Molecular neurobiology · 2025Review
- Partners in health and disease: pineal gland and purinergic signalling.Purinergic signalling · 2025Review
- The immunological landscape of traumatic brain injury: insights from pathophysiology to experimental models.Frontiers in neurology · 2025Review
- Microglial Response to Inflammatory Stimuli Under Electromagnetic Field Exposure.Archives of clinical and biomedical research · 2025Article
- Microglia-mediated neuroinflammation in traumatic brain injury: a review.Molecular biology reports · 2024Review
- Disease-relevant upregulation of P2YNature communications · 2024Article
- Astrocyte reactivity and inflammation-induced depression-like behaviors are regulated by Orai1 calcium channels.Nature communications · 2023Article
- Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats.Experimental and therapeutic medicine · 2023Article
- P2Y1 Receptor as a Catalyst of Brain Neurodegeneration.NeuroSci · 2022Review
- A multilayer network model of neuron-astrocyte populations in vitro reveals mGluRNetwork neuroscience (Cambridge, Mass.) · 2022Article
- Roles of Cytokines in the Temporal Changes of Microglial Membrane Currents and Neuronal Excitability and Synaptic Efficacy in ATP-Induced Cortical Injury Model.International journal of molecular sciences · 2021Article
- Pannexin-1 Channels as Mediators of Neuroinflammation.International journal of molecular sciences · 2021Review
- Regional NeurodegenerationFrontiers in computational neuroscience · 2021Article
- Targeting Neuroinflammation via Purinergic P2 Receptors for Disease Modification in Drug-Refractory Epilepsy.Journal of inflammation research · 2021Review
- Myeloid Pannexin-1 mediates acute leukocyte infiltration and leads to worse outcomes after brain trauma.Journal of neuroinflammation · 2020Article
- Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury.Cell communication and signaling : CCS · 2020Review
- Distinct P2Y Receptors Mediate Extension and Retraction of Microglial Processes in Epileptic and Peritumoral Human Tissue.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Context-Specific Switch from Anti- to Pro-epileptogenic Function of the P2YThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The recent public awareness of the incidence and possible long-term consequences of traumatic brain injury only heightens the need to develop effective approaches for treating this neurological disease. In this report, we identify a new therapeutic target for traumatic brain injury by studying the role of astrocytes, rather than neurons, after neurotrauma. We use in vivo multiphoton imaging and show that mechanical forces during trauma trigger intercellular calcium waves throughout the astrocytes, and these waves are mediated by purinergic signalling. Subsequent in vitro screening shows that astrocyte signalling through the 'mechanical penumbra' affects the activity of neural circuits distant from the injury epicentre, and a reduction in the intercellular calcium waves within astrocytes restores neural activity after injury. In turn, the targeting of different purinergic receptor populations leads to a reduction in hippocampal cell death in mechanically injured organotypic slice cultures. Finally, the most promising therapeutic candidate from our in vitro screen (MRS 2179, a P2Y1 receptor antagonist) also improves histological and cognitive outcomes in a preclinical model of traumatic brain injury. This work shows the potential of studying astrocyte signalling after trauma to yield new and effective therapeutic targets for treating traumatic brain injury.
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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 OpenQuestion graph.