Gordon R Ya, Shubina L V, Kapralova M V, Pershina E B, Khutzian S S, Arhipov V I
Tsitologiia. 2014;56(12):919-25.
Comparison between results of different ways of application of excitotoxin (kainic acid, KA), intrahippocampal (0.2 μg/μl) and intraventricular (0.6 μg/μl), was carried out in the course of investigations of the prolonged action of KA on the morphological state of various fields in dorsal hippocampus. Light microscopy with Cresyl Violet staining and fluorescent microscopy with staining by fluoro-jade B were used in our researches. The results revealed that KA, being injected intrahippocampally at a dose, which does not result in animal epileptization, caused obvious degenerative phenomena in hippocampus. Two weeks after KA injection the layers of pyramid cells in the fields CA3 and CA4 were absent, and in four weeks, degenerative changes and cell lysis were spread on the CA1 field as well. Four weeks after KA intraventricular administration in rats with epileptic status the damages of various levels were observed in hippocampus, from partial injuries of pyramid neurons in the fields CA3 and CA4 up to full loss of layers of pyramids in the fields CA1, CA3 and CA4. In both ways of KA injection, in the CA2 field the layer of cells mainly remained undamaged what indicates a special role of this field. After a single-time KA administration the both ways of injection led to the long-term damages of a neural tissue, possibly, of a general character, but differing in rates of neuron reactions in different fields to the damaging factor. An explanation of the prolonged action of KA excitotoxicity might be in the activation of GluR6-containing kainate receptors in pyramid neurons in CA3 field which brings to chronic character in single-time KA action and promotes the destruction of the remaining neurons by necrotic way while at the initial stage of KA influence the neurons perish by apoptotic way.
在研究兴奋性毒素(海藻酸,KA)对背侧海马不同区域形态状态的长期作用过程中,对不同给药方式(海马内注射,剂量为0.2μg/μl;脑室内注射,剂量为0.6μg/μl)的结果进行了比较。我们的研究采用了甲酚紫染色的光学显微镜和氟玉髓B染色的荧光显微镜。结果显示,海马内注射不会导致动物癫痫发作剂量的KA,可在海马中引起明显的退行性现象。KA注射两周后,CA3和CA4区的锥体细胞层消失,四周后,退行性变化和细胞溶解也蔓延至CA1区。在癫痫持续状态的大鼠脑室内注射KA四周后,海马出现了不同程度的损伤,从CA3和CA4区锥体细胞的部分损伤到CA1、CA3和CA4区锥体层的完全丧失。在两种KA注射方式中,CA2区的细胞层主要保持未受损,这表明该区域具有特殊作用。单次注射KA后,两种注射方式均导致神经组织的长期损伤,可能具有一般性,但不同区域的神经元对损伤因素的反应速度不同。KA兴奋性毒性长期作用的一个解释可能是,CA3区锥体细胞中含GluR6的海人藻酸受体被激活,这使得单次KA作用具有慢性特征,并促进剩余神经元通过坏死方式被破坏,而在KA作用的初始阶段,神经元通过凋亡方式死亡。