Reduced neurogenesis after neonatal seizures
Reduced neurogenesis after neonatal seizures
复制标题
DOI：
10.1523/jneurosci.21-06-02094.2001
复制
发表时间：
2001-03-15
影响因子：
5.3
通讯作者：
Holmes, GL
中科院分区：
文献类型：
--
作者：
McCabe, BK;Silveira, DC;Holmes, GL
虽然新生儿癫痫相当常见，但对其后果仍存在争议。尽管有相当多的证据表明，与成熟动物相比，癫痫发作可能导致幼年动物较少的细胞损失，但仍有明确的迹象表明，癫痫发作可能有其他潜在的有害影响。由于已知成熟大脑中的癫痫发作可以增加海马区的神经发生，因此我们研究了在出生后第0天(P0)到第四天(P4)期间进行一系列25次氟乙基诱发癫痫发作后，齿状回颗粒细胞层神经发生的程度。新生癫痫大鼠在注射BrdU后36小时或2周处死，其齿状回和门区胸腺嘧啶核苷类似物5-溴-2‘-脱氧尿苷-5’-单磷酸(BrdU)标记细胞数较对照组明显减少。最后一次癫痫发作后，BrdU标记细胞的减少持续到6d。BrdU标记的细胞主要与神经元标志物神经元特异性核蛋白共存，很少与胶质细胞标志物胶质纤维酸性蛋白共存，这表明新形成的细胞中有很大比例是神经元。单次癫痫发作的未成熟大鼠在BrdU标记的细胞数量上与对照组没有区别。相比之下，与对照组相比，成年大鼠经历了一系列25次氟乙基诱发的癫痫发作后，神经再生显著增加。本研究表明，新生大鼠反复癫痫发作后，新生颗粒细胞减少。
Although neonatal seizures are quite common, there is controversy regarding their consequences. Despite considerable evidence that seizures may cause less cell loss in young animals compared with mature animals, there are nonetheless clear indications that seizures may have other potentially deleterious effects. Because it is known that seizures in the mature brain can increase neurogenesis in the hippocampus, we studied the extent of neurogenesis in the granule cell layer of the dentate gyrus over multiple time points after a series of 25 flurothyl-induced seizures administered between postnatal day 0 (P0) and P4. Rats with neonatal seizures had a significant reduction in the number of the thymidine analog 5-bromo-2'-deoxyuridine- 5'-monophosphate- (BrdU) labeled cells in the dentate gyrus and hilus compared with the control groups when the animals were killed either 36 hr or 2 weeks after the BrdU injections. The reduction in BrdU-labeled cells continued for 6 d after the last seizure. BrdU-labeled cells primarily colocalized with the neuronal marker neuron-specific nuclear protein and rarely colocalized with the glial cell marker glial fibrillary acidic protein, providing evidence that a very large percentage of the newly formed cells were neurons. Immature rats subjected to a single seizure did not differ from controls in number of BrdU-labeled cells. In comparison, adult rats undergoing a series of 25 flurothyl-induced seizures had a significant increase in neurogenesis compared with controls. This study indicates that, after recurrent seizures in the neonatal rat, there is a reduction in newly born granule cells.