The intra-arterial injection of microglia protects hippocampal CA1 neurons against global ischemia-induced functional deficits in rats
The intra-arterial injection of microglia protects hippocampal CA1 neurons against global ischemia-induced functional deficits in rats
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DOI：
10.1016/j.neuroscience.2006.06.003
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发表时间：
2006-09-29
期刊：
影响因子：
3.3
通讯作者：
Nakanishi, H.
中科院分区：
文献类型：
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作者：
Hayashi, Y.;Tomimatsu, Y.;Nakanishi, H.
在本研究中，我们试图阐明动脉内注射小胶质细胞对全脑缺血诱导的海马CA 1神经元功能和形态缺陷的影响。当PKH 26标记的永生化小胶质细胞，GMIR 1，注射到锁骨下动脉，这些外源性小胶质细胞被发现在缺血后24小时在海马中积累。在海马切片中，从中注射大鼠缺血48小时前，突触功能障碍，包括突触反应的显着减少和显着减少的长时程增强（LTP）的CA 3-CA 1谢弗侧支突触进行了观察。然而，在这个阶段，在海马中既没有观察到显著的神经元变性也没有观察到神经胶质增生。缺血后96 h，CA 1区突触活动完全丧失，神经元明显死亡。相反，在从注射小胶质细胞的动物制备的切片中，缺血后CA 3-CA 1突触的基础突触传递和LTP得到很好的保留。我们还发现，小胶质细胞条件培养基（MCM），以显着增加自发突触后电流的CA 1神经元的频率，而不影响振幅，从而表明MCM增加了神经递质释放的可证明性。通过免疫组化和免疫印迹分析证实了动脉内注射小胶质细胞对缺血诱导的海马神经元变性的保护作用。此外，动脉注射的小胶质细胞防止缺血引起的脑源性神经营养因子（BDNF）在CA 1神经元水平的下降。这些观察结果强烈表明，动脉注射小胶质细胞保护CA 1神经元对缺血诱导的神经元变性。缺血诱导的突触缺陷的恢复和由此导致的CA 1神经元中BDNF水平的降低，可能通过释放扩散因子，因此可能有助于动脉注射小胶质细胞对抗缺血诱导的神经元变性的保护作用。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
In the present study, we have attempted to elucidate the effects of the intra-arterial injection of microglia on the global ischemia-induced functional and morphological deficits of hippocampal CA1 neurons. When PKH26-labeled immortalized microglial cells, GMIR1, were injected into the subclavian artery, these exogenous microglia were found to accumulate in the hippocampus at 24 h after ischemia. In hippocampal slices prepared from medium-injected rats subjected to ischemia 48 h earlier, synaptic dysfunctions including a significant reduction of synaptic responses and a marked reduction of long-term potentiation (LTP) of the CA3-CA1 Schaffer collateral synapses were observed. At this stage, however, neither significant neuronal degeneration nor gliosis was observed in the hippocampus. At 96 h after ischemia, there was a total loss of the synaptic activity and a marked neuronal death in the CA1 subfield. In contrast, the basal synaptic transmission and LTP of the CA3-CA1 synapses were well preserved after ischemia in the slices prepared from the microglia-injected animals. We also found the microglial-conditioned medium (MCM) to significantly increase the frequency of the spontaneous postsynaptic currents of CA1 neurons without affecting the amplitude, thus indicating that MCM increased the provability of the neurotransmitter release. The protective effect of the intra-arterial injected microglia against the ischemia-induced neuronal degeneration in the hippocampus was substantiated by immunohistochemical and immunoblot analyses. Furthermore, the arterial-injected microglia prevented the ischemia-induced decline of the brain-derived neurotrophic factor (BDNF) levels in CA1 neurons. These observations strongly suggest that the arterial-injection of microglia protected CA1 neurons against the ischemia-induced neuronal degeneration. The restoration of the ischemia-induced synaptic deficits and the resultant reduction of the BDNF levels in CA1 neurons, possibly by the release of diffusible factor(s), might thus contribute to the protective effect of the arterial-injection of microglia against ischemia-induced neuronal degeneration. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.