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Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats

Liu, X; Zhao, Z; Ji, R; Zhu, J; Sui, Q-Q; Knight, GE; Burnstock, G; ... Xiang, Z; + view all (2017) Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats. Purinergic Signalling , 13 (4) pp. 529-544. 10.1007/s11302-017-9579-y. Green open access

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Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability for people under the age of 45 years worldwide. Neuropathology after TBI is the result of both the immediate impact injury and secondary injury mechanisms. Secondary injury is the result of cascade events, including glutamate excitotoxicity, calcium overloading, free radical generation, and neuroinflammation, ultimately leading to brain cell death. In this study, the P2X7 receptor (P2X7R) was detected predominately in microglia of the cerebral cortex and was up-regulated on microglial cells after TBI. The microglia transformed into amoeba-like and discharged many microvesicle (MV)-like particles in the injured and adjacent regions. A P2X7R antagonist (A804598) and an immune inhibitor (FTY720) reduced significantly the number of MV-like particles in the injured/adjacent regions and in cerebrospinal fluid, reduced the number of neurons undergoing apoptotic cell death, and increased the survival of neurons in the cerebral cortex injured and adjacent regions. Blockade of the P2X7R and FTY720 reduced interleukin-1βexpression, P38 phosphorylation, and glial activation in the cerebral cortex and improved neurobehavioral outcomes after TBI. These data indicate that MV-like particles discharged by microglia after TBI may be involved in the development of local inflammation and secondary nerve cell injury.

Type: Article
Title: Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s11302-017-9579-y
Publisher version: http://dx.doi.org/10.1007/s11302-017-9579-y
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Microglial cells, Microvesicles, Neuroinflammation, P2X7R, Traumatic brain injury
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1573181
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