Protective Roles And Mechanisms Of Adenosine A1 Receptor In Cerebral Neuronal Damage Induced By Hypoxia And Reoxygenation

The present studies were conducted to evaluate the effects of selective adenosine Al receptor antagonist DPCPX on neuronal damage induced by hypoxia and reoxygenation and its probable mechanisms,and to investigate the effects of DPCPX on astrocytic neuroprotection following hypoxia and reoxygenation.The effects of hypoxic preconditioning on adenosine Al receptor protein expression in neurons and astrocytes were also explored.We investigated the effect of DPCPX on cell injury in neurons induced by hypoxia and reoxygenation and its mechanism,detected the change of adenosine Al receptor protein expression in neurons following hypoxic preconditioning.The results showed DPCPX aggravated cell injury,moreover,a significant decrease of Bcl-2 protein expression,antioxidation ability,extracellular content ofγ-aminoburytic acid,activity of Ca²⁺,Mg²⁺-ATPase,Ca²⁺-ATPase and a specific increase of level of NO,activity of inducible NOS,calcineurin and acetylcholinesterase in neurons following hypoxia and reoxygenation were observed.In addition,we found hypoxic preconditioning dramatically upregulated the expression of neuronal adenosine Al receptor protein.After investigating exogenous lactic acid and astrocyte-derived lactic acid on neuronal injury induced by hypoxia and reoxygenation,we explored the effect of hypoxic preconditioning and DPCPX on the release of lactic acid from astrocyte,the results showed astrocyte-derived lactic acid aggravated neuronal damage and hypoxic preconditioning decreased wheras DPCPX had no obvious influence on the release of lactic acid from astrocyte after hypoxia and reoxygenation.Moreover,we found DPCPX reduced the release of erythropoietin and 17βestradiol from astocytes and attenuated the activity of glutamine synthase,superoxide dimutase and glutathione peroxidase in astrocytes following hypoxia and reoxygenation.In addition,the results indicated hypoxic preconditioning dramatically upregulated the expression of adenosine Al receptor protein in astrocytes.Above all,adenosine Al receptor can mediate the protective role of adenosine in neurons during hypoxia and reoxygenation,its mechanism might involve the increase of Bcl-2 protein expression,antioxidation ability,extracellularγ-aminoburytic acid, activity of Ca²⁺,Mg²⁺-ATPase and Ca²⁺-ATPase,DPCPX can enhance the activity of calcineurin and acetylcholinesterase,its mechanism is awaited to be elucidated, adenosine Al receptor may be involved in erythropoietin and 17βestradiol release from astrocyte and the maintainence of activity of glutamine synthase,superoxide dimutase and glutathione peroxidase in astrocytes to strengthen astrocytic neuroprotection following hypoxia and reoxygenation.The upregulation of adenosine Al receptor protein in neurons and astrocytes suggests its participation in neuroprotection induced by transient hypoxic preconditioning.