Induction of infarct tolerance by platelet-derived growth factor against temporary focal ischemia
Induction of infarct tolerance by platelet-derived growth factor against temporary focal ischemia
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DOI：
10.1016/s0006-8993(97)01345-0
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发表时间：
1998-02-16
期刊：
影响因子：
2.9
通讯作者：
Kikuchi, H
中科院分区：
文献类型：
--
作者：
Sakata, M;Yanamoto, H;Kikuchi, H
神经生长因子、脑源性神经营养因子和其他神经营养因子已被报道对全脑缺血具有神经保护作用。为了研究血小板衍生生长因子B链（PDGF-BB）的同源二聚体是否可以保护神经元免受局灶性暂时性缺血，在缺血之前、期间和之后将PDGF-BB施用至大鼠脑持续延长的时间，因为在我们先前的研究中PDGF-BB保护大鼠神经元免受全脑缺血。总共使用82只雄性Sprague-Dawley大鼠，重组PDGF-BB，或盐水通过植入的渗透泵给药到左侧新皮层中，在缺血前和缺血后2天给药3天（总共1.2 μ g）、7天（总共2 μ g或4 μ g）或14天（总共4 μ g）。在另一组中，通过渗透泵给药PDGF-BB（共4 μ g）14天，在移除泵后再间隔7天诱导局灶性缺血。通过双侧CCA和MCA闭塞2小时，在左侧MCA区域诱导局灶性暂时缺血。缺血后2天处死所有大鼠，TTC染色分析脑梗死体积。在另一组动物中，脑内给予PDGF-BB或生理盐水14天后，通过氢清除法和新皮质的激光多普勒血流仪（LDF）监测局部脑血流量（rCBF）。在缺血前接受PDGF-BB（共4 μ g）7或14天的组中，与对照组或盐水输注组相比，新皮质梗死显著减少。脑梗死的大小是最小的组中，接受PDGF-BB的14天，当缺血引起的7天后，删除泵。对于rCBF测量，接受PDGF-BB或生理盐水输注14天的组中没有显著差异。在局灶性缺血模型中也证实了PDGF-BB对全脑缺血的有效神经保护作用。然而，延长脑内灌注7至14天是必要的，以实现梗死体积的显着减少。神经保护不是由于缺血时侧支血流增加。(C)1998年Elsevier Science B.V.
Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet-derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study, A total of 82 male Sprague-Dawley rats were used, Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 mu g in total), 7 days (2 mu g or 4 mu g in total), or 14 days (4 mu g in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF-BB (4 mu g in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF-BB or saline. In the group receiving PDGF-BB (4 mu g in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF-BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF-BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia. (C) 1998 Elsevier Science B.V.