The Roles And Mechanism Of Adenosine A2A Receptors In Acute Stage Of Traumatic Brain Injury

Traumatic brain injury (TBI) is severely harmful to human's health in modern society. TBI includes primary injury and secondary injury. The primary injury, such as bone fracture and intracranial hemorrhage, could be well cured by surgical intervention. The secondary injury includes glutamate excitotoxicity, uncontrolled inflammatory responses, oxygen free radical stress, and so on. It is the main reason of brain injury. But it is also a hard point in clinic therapy up to now.Adenosine level rises markedly in the extracellular fluid of the brain as ATP breakdown in response to many insults including TBI. A2AR is one of the four adenosine receptors. Interestingly, activation of A2AR may contribute to both neural injury and protection in several neurological disease models. In TBI models, it is not well known that activation of A2ARs can protect against or aggravate the injury.1. The effect of pharmacological intervention of A2AR on TBICaffeine is a non-selective adenosine receptor antagonist. It prefers to prevent the roles of A2A receptor in low dose. CGS21680 is a selective A2AR agonist.In this study, the effects of caffeine or CGS21680 administration on TBI, which were induced by controlled cortical impact in KM mice, were examined.Methods: KM mice were divided into four treatment groups: (1) water treatment; (2) oral caffeine (0.25 g/L) for 3 weeks before TBI; (3) acute intraperitoneal injection of caffeine (15mg/kg) 30 minutes before TBI;(4)acute intraperitoneal injection of CGS21680(0.1mg/kg) 30 minutes before TBI. The mice were then subjected to controlled cortical impact (CCI) or no-CCI. CCI was performed by dropping a 20.0g-weight from 50 cm height onto the brain. The level of glutamate in cerebral spinal fluid (CSF) and the mRNA expression of inflammatory factors (TNF-α,IL-1β) in injured brain tissue were determined at 12 hours post-TBI. The neurological deficit score and brain water contents were determinated at 24 hours post-TBI.Results: Twenty-hour hours after TBI, the brain water contents of the injured cerebral...