Abstract：Objective To investigate the effect of adenosine A2A receptor on pituitary-adrenal axis response in acute phase of moderate craniocerebral trauma.Methods Eighteen adenosine A2A receptor knock-out mice in a C57BL/6 background and another eighteen their wild-type littermates were divided into normal control group and craniocerebral trauma for 4 hours group,and craniocerebral trauma for 24 hours group according to random number table,with siμ mice per group.Plasma levels of adrenocorticotropic-hormone (ACTH) and corticosterone at hours 4 and 24 postinjury were determined using ELISA method.Results At 4 and 24 hours,brain water content in wild-type mice [(80.950 ± 0.184) ％,(82.178 ± 0.255)％ respectively] was higher than that in gene knock-out mice [(80.006 ± 0.199)％,(81.091 ± 0.295)％ respectively,P ＜ 0.01].Besides,brain water content in both wild-type and gene knock-out mice increased after injury (P ＜ 0.01).Plasma levels of ACTH and corticosterone were higher in geneknock-out sham mice than in wild-type sham mice [(120.214 ± 2.472) ng/L vs (91.767 ±7.395) ng/L,(27.814 ±0.888) μg/L vs (11.430 ±0.644) μg/L respectively,P ＜0.0l].At 4 and 24 hours,plasma levels of ACTH [(174.776-± 5.040) ng/L,(189.613 ± 4.802) ng/L respectively] in geneknock-out mice showed a higher increase than those in wild-type mice [(119.594 ± 6.945) ng/L,(124.93-± 11.001 7) ng/L respectively,P ＜ 0.05].Moreover,plasma levels of corticosterone [(40.138 ±-0.805) μg/L] at 4 hours and [(37.440-0.485)μg/L] at 24 hours in gene knock-out mice showed a same result as compared with that in wild-type mice [(19.702 ± 0.804) μg/L,(17.602 ± 0.743) μg/L respectively,P ＜ 0.05].Conclusions Knock-out of adenosine A2A receptor increases the release of ACTH and corticosterone in acute stage of moderate craniocerebral trauma and promotes pituitary-adrenal stress response.This may provide a novel explanation for the neuroprotective effect of A2A receptor deficiency.
. Effect of adenosine A2A receptor on stress response of pituitaryadrenal axis in acute phase of craniocerebral trauma in mice[J]. CHINESE JOURNAL OF TRAUMA, 2013, 29(12): 1236-1239.
［1］Powner DJ,Boccalandro C,Alp MS,et al. Endocrine failure after traumatic brain injury in adults.Neurocrit Care,2006,5(1):61-70.
［2］Kell CA,Stehle JH.Just the two of us: melatonin and adenosine in rodent pituitary function.Ann Med,2005,37(2):105-120.
［3］Lusardi TA. Adenosine neuromodulation and traumatic brain injury.Curr Neuropharmacol,2009,7(3):228-237.
［4］Dai SS,Zhou YG,Li W,et al.Local glutamate level dictates adenosine A2A receptor regulation of neuroinflammation and traumatic brain injury.J Neurosci,2010,30(16):5802-5810.
［5］Slivka A, Murphy E, Horrocks L. Cerebral edema after temporary and permanent middle cerebral artery occlusion in the rat. Stroke,1995,26(6):1061-1066.
［6］Nicholson SA. Stimulatory effect of caffeine on the hypothalamo-pituitary-adrenocortical axis in the rat. J Endocrinol,1989,122(2):535-543.
［8］Buttgereit F, Burmester GR, Lipworth BJ. Optimised glucocorticoid therapy: the sharpening of an old spear. Lancet, 2005, 365(9461):801-803.
［9］Abrahám I, Harkany T, Horvath KM, et al. Chronic corticosterone administration dose-dependently modulates Abeta(1-42)- and NMDA-induced neurodegeneration in rat magnocellular nucleus basalis. J Neuroendocrinol, 2000, 12(6):486-494. 〖ZK)〗
［10］Tsuruma K, Nakagawa T, Morimoto N, et al. Glucocorticoid modulatory element-binding protein 1 binds to initiator procaspases and inhibits ischemia-induced apoptosis and neuronal injury. J Biol Chem, 2006, 281(16):11397-11404.
［11］Englander J,Bushnik T,Oggins J,et al.Fatigue after traumatic brain injury: Association with neuroendocrine, sleep, depression and other factors.Brain Inj,2010,24(12):1379-1388.
［12］Farrar AM, Segovia KN, Randall PA, et al. Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and dopamine D2 receptors. Neuroscience, 2010, 166(4):1056-1067.
