Giorgi Filippo S, Pizzanelli Chiara, Biagioni Francesca, Murri Luigi, Fornai Francesco
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56100 Pisa, Italy.
Neurosci Biobehav Rev. 2004 Sep;28(5):507-24. doi: 10.1016/j.neubiorev.2004.06.008.
This article provides a brief review of the role of norepinephrine (NE) in epilepsy, starting from early studies reproducing the kindling model in NE-lesioned rats, through the use of specific ligands for adrenergic receptors in experimental models of epilepsy, up to recent advances obtained by using transgenic and knock-out mice for specific genes expressed in the NE system. Data obtained from multiple experimental models converge to demonstrate the antiepileptic role of endogenous NE. This effect predominantly consists in counteracting the development of an epileptic circuit (such as in the kindling model) rather than increasing the epileptic threshold. This suggests that NE activity is critical in modifying epilepsy-induced neuronal changes especially on the limbic system. These data encompass from experimental models to clinical applications as recently evidenced by the need of an intact NE innervation for the antiepileptic mechanisms of vagal nerve stimulation (VNS) in patients suffering from refractory epilepsy. Finally, recent data demonstrate that NE loss increases neuronal damage following focally induced limbic status epilepticus, confirming a protective effect of brain NE, which has already been shown in other neurological disorders.
本文简要回顾了去甲肾上腺素（NE）在癫痫中的作用，从早期在NE损伤大鼠中重现点燃模型的研究，到在癫痫实验模型中使用肾上腺素能受体的特异性配体，直至利用NE系统中表达的特定基因的转基因和基因敲除小鼠所取得的最新进展。从多个实验模型获得的数据一致证明内源性NE的抗癫痫作用。这种作用主要在于抵消癫痫回路的发展（如在点燃模型中），而非提高癫痫阈值。这表明NE活性在改变癫痫诱导的神经元变化方面至关重要，尤其是对边缘系统。这些数据涵盖了从实验模型到临床应用，最近有证据表明，难治性癫痫患者迷走神经刺激（VNS）的抗癫痫机制需要完整的NE神经支配。最后，最近的数据表明，NE缺失会增加局灶性诱导的边缘性癫痫持续状态后的神经元损伤，证实了脑NE的保护作用，这在其他神经系统疾病中也已得到证明。
