Knockdown TNFa Expression By Antisense Oligodeoxynucleotide In Early Stage Of Transient Focal Brain Ischemia

[Background and purpose] It has been well established that inflammatory reaction accompanies cerebral ischemia. Tumor necrosis factor-alpha(TNFa) and interleukin-1 P play a pivotal role in inducing the inflammatory process and work in synergic manner. According to current knowledge, the role of TNFais complex. It exhibits neuroprotective function as well as neurotoxicity. At the same time when TNFacauses inflammatory damage to ischemia tissue, it also activate tissue regeneration and induce antioxidative reaction. The role of TNFa is controversial now. Here the authors studies the effect of an antisense oligodeoxynucleotide(ODN) named TJU-2577 directed against the TNFa in a transient focal cerebral ischemia model in SD rat. <>[methods] The intracerebroventricuTar administration of ODN or artificial cerebroventricular fluid (ASCF) was initiated 36-hours before induction of cerebral ischemia and repeated at 12-hours interval. Each injection contains 20ug ODN or ASCF. The 4th injection was performed 12-hours after induction of cerebral ischemia. After the 3rd injection, the rat was immediately subjected to transient left MCAO and reperfusion began after 70-minutes.[result and conclusion] When compared with animals treated with vehicle or an sense ODN named TJU-2755ss, the antisense ODN TJU-2755 reduced the infarction volume by 20%' and significantly improved recovery of sensorimotor function. The current study revealed that antisense ODN selectively inhibit the expression of TNFa by local brain tissue after transient focal brain ischemia in rat. In addition, the inhibition of TNFa at early stage of cerebra ischemia is neuroprotective. We provide new evidence that TNFa is involved in cerebral ischemic damage. We concluded that at early stage of cerebral ischemia, the dominant role of TNFa is induce inflammatory damage to ischemic tissue.