Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats.
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.
['Liu|Xiaofeng|X|', 'Zhao|Zhengqing|Z|', 'Ji|Ruihua|R|', 'Zhu|Jiao|J|', 'Sui|Qian-Qian|QQ|', 'Knight|Gillian E|GE|', 'Burnstock|Geoffrey|G|', 'He|Cheng|C|', 'Yuan|Hongbin|H|', 'Xiang|Zhenghua|Z|http://orcid.org/0000-0001-7891-5305']
D000818:Animals D000070642:Brain Injuries, Traumatic D055252:Cell-Derived Microparticles D006146:Guanidines D008297:Male D017628:Microglia D058920:Purinergic P2X Receptor Antagonists D011804:Quinolines D011897:Random Allocation D051381:Rats D017207:Rats, Sprague-Dawley D058486:Receptors, Purinergic P2X7
Traumatic brain injury Neuroinflammation P2X7R Microglial cells Microvesicles