Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Munich, Germany.
Hippocampus. 2011 Aug;21(8):866-76. doi: 10.1002/hipo.20802. Epub 2010 Jun 1.
Changes in the rate of dentate granule cell neurogenesis and in the fate of newborn granule cells have been implicated in the development and progression of epilepsies. Strategies to normalize neurogenesis in chronic epilepsy models are thought to increase our understanding of the functional consequences of aberrant neurogenesis in the epileptic brain. Therefore, we modulated neurogenesis in an amygdala kindling paradigm in rats by targeted irradiation of the hippocampus using a medical linear accelerator device. Selective irradiation normalized the hippocampal cell proliferation rate in kindled animals. Both, in kindled and nonkindled rats the number of BrdU/NeuN-labeled newborn neurons was reduced in response to irradiation. Whereas kindling resulted in a pronounced increase in the number of neuroblasts identified based on doublecortin-labeling, irradiation prevented the expansion of the neuroblast population. Moreover, irradiation counteracted the kindling-associated increase in hilar basal dendrites, and kept the fraction of cells with basal dendrites at control levels. Despite the efficacious modulation of neurogenesis, irradiation did not affect the rate of kindling progression. Both, the number of stimulations as well as the cumulative afterdischarge duration to reach respective seizure stages were comparable in animals with and without irradiation. In addition, pre- and postkindling thresholds as well as seizure parameters recorded at threshold stimulation remained unaffected by irradiation. In conclusion, the fact that the efficacious modulation of neurogenesis by irradiation did not exert any effects on kindling acquisition and kindled seizures suggests that newborn neurons do not critically contribute to the hyperexcitable state in the chronic epilepsy model used.
齿状回颗粒细胞神经发生率的变化和新生颗粒细胞的命运变化被认为与癫痫的发展和进展有关。在慢性癫痫模型中，使神经发生正常化的策略被认为可以增加我们对癫痫脑中异常神经发生的功能后果的理解。因此，我们通过使用医用线性加速器设备对海马体进行靶向照射，来调节杏仁核点燃模型中的神经发生。选择性照射使点燃动物的海马细胞增殖率正常化。在点燃和未点燃的大鼠中，BrdU/NeuN 标记的新生神经元数量都因照射而减少。虽然点燃导致双皮质素标记的神经前体细胞数量显著增加，但照射阻止了神经前体细胞群体的扩张。此外，照射抵消了点燃相关的内嗅区基底树突的增加，并使具有基底树突的细胞分数保持在对照水平。尽管神经发生的有效调节，但照射并没有影响点燃进展的速度。无论是在有照射和无照射的动物中，刺激的次数以及达到各自癫痫阶段的累积后放电持续时间都是可比的。此外，照射对预点燃和点燃阈值以及在阈值刺激下记录的癫痫参数没有影响。总之，照射对神经发生的有效调节并没有对点燃获得和点燃性癫痫发作产生任何影响，这表明新生神经元对所使用的慢性癫痫模型中的过度兴奋状态没有关键贡献。
