Department of Neurological Surgery and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Epilepsy Res. 2013 May;104(3):226-33. doi: 10.1016/j.eplepsyres.2012.11.002. Epub 2012 Dec 3.
Cortical dysplasia (CD) is strongly associated with intractable epilepsy, probably due to hyperexcitability of neuronal networks. However, the underlying mechanisms are not completely understood. GABAergic interneurons provide major inhibitory function in the CNS and have different subtypes, but it is not clear how each subtype is affected in CD during early post-natal development. We have examined the developmental alterations of the densities of two major subtypes of interneurons, parvalbumin (PV)- and somatostatin (SS)-expressing interneurons in an animal model of CD, in utero irradiation, using immunocytochemistry. We found that the density of PV- and SS-positive interneurons increases significantly in CD and controls during the first three weeks of postnatal life. However, compared to controls, the densities of both subtypes are significantly decreased in CD and heterotopia at all age groups although the time of onset for both PV and SS expression remained unchanged. Our results indicate that the densities of both PV- and SS-positive interneurons are significantly decreased in CD and heterotopia, which may be one important mechanism leading to hyperexcitability of CD.
皮质发育不良（CD）与难治性癫痫密切相关，可能是由于神经元网络的过度兴奋。然而，其潜在的机制尚不完全清楚。γ-氨基丁酸能中间神经元在中枢神经系统中提供主要的抑制功能，并且具有不同的亚型，但尚不清楚在 CD 中每个亚型在出生后早期发育过程中是如何受到影响的。我们使用免疫细胞化学技术，在宫内照射的 CD 动物模型中，研究了两种主要中间神经元亚型——表达 parvalbumin（PV）和 somatostatin（SS）的中间神经元密度的发育变化。我们发现，在出生后第一至三周，CD 和对照组的 PV-和 SS-阳性中间神经元密度显著增加。然而，与对照组相比，在所有年龄组中，CD 和异位的两种亚型的密度均显著降低，尽管 PV 和 SS 表达的起始时间保持不变。我们的结果表明，CD 和异位的 PV-和 SS-阳性中间神经元密度显著降低，这可能是导致 CD 过度兴奋的一个重要机制。
