Neuroprotection By Aspirin Following Transient Global Ischemia In Rats

Emerging studies now suggest that cerebral ischemia can induce delayed neuronal death (DND). The three pathophysiological processes of calcium influx, oxidative stress, and glutamate toxicity have all been proposed to mediate ischemic DND. With the development of molecular biology, it demonstrated that apoptosis participate in DND induced by ischemia. Nuclear transcription factor kappa B (NF- K B) is central controller in TNFR and DR3 signaling. When activated, this multisubunit transcription factor induces the expression of genes encoding acute-phase proteins, therefore promote cell death. It has not been understood about the function of NF- K B following cerebral ischemia, whereas the fact of activation of it implied in recent. Neuroprotective agents, is increasingly becoming the focus of brain research involving ischemia. There has not been ideal drug curing cerebral ischeniia in clinic by far although some reagents are effective in animal and preclinical tests. Acetylsalicylic acid(Aspirin, ASA), a classic pain-relieve agent, has been founded to posses the neuroprotective effect which connected with the repression of activation of NF- K B in neurons. The action of ASA on global cerebral ischemia has not been achieved up to now, which brings our study on it. Pulsinelli抯 four-vessel occlusion model was made on adult male Wistar rats. The animals were subjected 15 minutes global ischernia and different durations of reperfusion (24,48,72,168 hours). Three dosages of ASA (10,40,100 mg/kg ?d) were administered orally for 3 days, with first dose given one hour before ischemia. With the methods of H.E staining, TUNEL and immunohistochemistry, we investigated the morphological changes of pyramidal neurons in CAl region and the effects of ASA on it. The relation between ASA and NF- K B in hippocampal CAl region was also examined. Investigation on morphological and interventional outcome. ?? DND of pyramidal neurons in CAl region was induced 24 hours after reperfusion following global ischemia. Apoptosis-shaped pyramidal cells were initially detected in CAl region at 24 hours after ischemia by TIJNEL staining and reached maximal at 72 hours. Its time schedule was consistent with DND.The morphological characteristic of these cells showed apoptotic changes involving condensed cytoplasm, pyknotic nuclei and intact cytomem-brane. Furthermore, ASA specially attenuated CAl pyramidal neuronal death in a concentration-dependent manner, which implied a neuroprotective effect of ASA on CAl pyramidal cell following transient global ischemia. Investigation on expression of NF桲 B p50 after ASA treatment. We found, (l)No positive expression of NF- K B was detected in sham-operated group. (2) Expression of NE- K B p50 was detected in many areas including cortex, white matter, thalamus and hippocampus 24~48 hours after reperfusion. Whereas, positive expression was detecthed only in injuried pyramidal cells of hippocampal CAl region 72 hours after reperfusion. (3) Positive TUNEL cell was consistent with NF- K B in part 48 hours after global ischetnia. (4) ASA selectively attenuated the expression of caspase-3 and NF- K B in CAl neurons it demonstrated that NE- K B were upregulated in pyramidal cells in hippocampal CAl region after reperfusion following global ischemia. The elevated expression of NE- K B promoted apoptosis of CAl cells, which...