[Intracerebroventricular administration of adenosine A1 receptor antisense oligodeoxynucleotide inhibites the neuroprotective effect of the cerebral ischemic preconditioning in rats]

To further explore the role of adenosine A1 receptor in the neuroprotective effect of cerebral ischemic preconditioning, the present study was undertaken to observe the effect of inhibiting expression of adenosine Al receptor with adenosine A1 receptor antisense oligodeoxynucleotide (ARA1 As-ODN) on the neuroprotective effect of cerebral ischemic preconditioning against delayed neuronal death (DND) normally induced by lethal brain ischemia.The rat 4-vessel occlusion global cerebral ischemic model was used. Forty-eight male Wistar rats with permanent occlusion of the bilateral vertebral arteries were divided into 8 groups: Sham, CIP, brain ischemic insult, CIP + brain ischemic insult, Distilled water + CIP + brain ischemic insult, ARA1 As-ODN, ARA1 As-ODN +CIP, ARA1 As-ODN+ CIP + brain ischemic insult(two doses of 10 nmol/5 microl and 20 nmol/5 microl were used) groups. ARA1 As-ODN was dissolved in distilled water and injected into the right lateral cerebral ventricle. To illustrate the profile of DND, histological grade (HG) and neuronal density (ND) in the CA1 region of the hippocampus were examined 7 d after the sham operation or the last time of ischemia under thionin staining.The HG and ND in CIP group were similar to those in sham group. Brain ischemic insult induced obvious DND as represented with the increase in HG and decrease in ND significantly (P0.05 vs. sham and CIP groups). In CIP + ischemic insult group,no obvious DND was observed,which indicated that CIP protected pyramidal neurons against the ischemic insult.While the administration of ARA1 As-ODN in ARA1 As-ODN + CIP + brain ischemic insult group caused obvious increase in HG and decrease in ND compared with CIP + brain ischemic insult group (P0.05) in a dose dependent manner,which indicated that the neuroprotective effect of CIP against DND of hippocampal pyramidal neurons normally induced by ischemic insult was inhibited by the administration of ARA1 As-ODN.The results further demonstrate the association of up-regulation of adenosine A1 receptors with the induction of CIP-mediated BIT.