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DBS对海人酸癫痫大鼠突触外GABAA受体亚基的影响

Keywords: 脑深部刺激,海人酸,突触外GABAA受体,致痫大鼠

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Abstract:

目的研究DBS治疗对海人酸癫痫大鼠大脑中突触外GABAA受体δ亚基分布与表达的影响,为癫痫的发病机制与DBS的治疗机制的研究提供参考。方法雄性SD大鼠24只,随机分为正常对照组、癫痫组、DBS治疗组。通过免疫组织化学方法检测突触外GABAA受体δ亚基在大鼠大脑中的分布与表达量的变化。结合大鼠脑电信号的采集分析以及病理形态学观察,分析DBS在癫痫治疗中的作用以及对突触外GABAA受体δ亚基的影响。结果DBS治疗组大鼠癫痫发作次数(6.01±4.87,n=8)明显低于癫痫对照(17.31±4.59,n=8),P<0.05;DBS治疗可有效抑制癫痫大鼠海马异常放电;DBS治疗组(463.62±38.41,n=8)大鼠海马神经元坏死及胶质细胞增生程度较癫痫组轻(357.12±20.50,n=8)(P<0.05);正常对照组大鼠脑组织突触外GABA受体δ亚基主要分布在海马(IOD=30.96±2.73,n=8)与丘脑腹外侧核(IOD=32.85±2.35,n=8)。癫痫组大鼠脑组织海马(IOD=12.31±1.72,n=8)及丘脑腹外侧核(IOD=22.39±1.94,n=8)突触外GABA受体δ亚基表达下降。DBS治疗组的丘脑腹外侧核(IOD=35.91±3.97,n=8),海马区(IOD=22.74±2.08,n=8)突触外GABA受体δ亚基表达比癫痫组表达增高(P<0.05)。结论丘脑底核DBS治疗可以通过改变大脑突触外GABA受体δ亚基的表达,抑制癫痫大鼠海马的异常放电,减轻癫痫大鼠海马神经元病理变化,起到对癫痫的治疗作用。

References

[1]  Engel J Jr, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures, Surgical Treatment of the Epilepsies [M]. 2nd ed. New York: Raven Press, 1993: 609?622.
[2]  Vitek JL. Deep brain stimulation: how does it work? [J]. Clinic Journal of Medicine, 2008,75(Suppl 2):S59-65.
[3]  Pugh JR, Raman IM. GABAA receptor kinetics in the cerebellar nuclei: evidence for detection of transmitter from distant release sites[J]. Biophysical Journal, 2005,88(3):1740-1754.
[4]  Peng Z, Huang CS, Stell BM, et al. Altered expression of the delta subunit of the GABAA receptor in a mouse model of temporal lobe epilepsy[J]. The Journal of Neuroscience, 2004,24(39):8629-8639.
[5]  Windels F, Bruet N, Poupard A,et a1. Influence of the frequency parameter on extracelluar glutamate and gamma aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic in rats[J]. Neurosci Res, 2003, 72(2):259-267.
[6]  Vercueil L, Benazzouz A, Deransart C, et al. High-frequency stimulation of the δ subthalamic nucleus suppresses absence seizures in the rat: comparison with neurotoxic lesions[J]. Epilepsy Res, 1998, 31:39-46.
[7]  Gjedde A, Geday J. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex [J]. Plosone, 2009,4(12):8120.
[8]  Bruet N, Poupard A, Feuerstein C, et al. Influence of the Frequency Parameter on Extracellular Glutamate and Gama Aminobutyric Acid in Substantia Nigra and Globus Pallidus During Electrical Stimulation of Subthalamic Franc [J]. Journal of Neuroscience Research, 2003,34:259-267.
[9]  Semyanov A, Walker MC, Kullmann DM, et al. Tonically active GABAA receptors: modulating gain and maintaining the tone [J]. Neurosciences, 2004,27(5):262-269.
[10]  Serwanski DR, Miralles CP, Christie SB, et al. Synaptic and non-synaptic localization of GABAA containing the α5 subunit in the rat brain receptors[J].J Comp Neurol, 2006, 499(3):458-470.
[11]  Houser CR, Esclapez M. Downregulation of the a 5 Subunit of the GABA A Receptor in the Pilocarpine Model of Temporal Lobe Epilepsy[J].Hippocampus, 2003,13(5): 633-645.
[12]  Thakkar MM, Winston S, McCarley RW. Effect of Microdialysis Perfusion of 4,5,6,7-Tetrahydroisoxazolo-
[13]  [5,4-C]pyridine-3-ol in the Perifornical Hypothalamus on Sleep-Wakefulness: Role of delta-Subunit Containing Extrasynaptic GABAA Receptors[J].Neuroscience, 2008,153(3):551-555.
[14]  Farrant M, Nusser Z. Variationa on an inhibitory theme:phasic and tonic activation of GABAA receptors[J].Neuroscience, 2005,6(3):215-230.
[15]  Semyanov A, Walker MC, Kullmann DM, et al. Tonically active GABA A receptors: modulating gain and maintaining the tone[J].Trends in Neurosciences,2004, 27(5):262-269.
[16]  Qi JS, Yao J, Fang C, et al, Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal cultures[J].J Physiol, 2006, 577(Pt 2): 579-590.
[17]  Peng Z, Huang CS, Stell BM, et al, Altered Expression of the delta Subunit of the GABA A Receptor in a Mouse Model of Temporal Lobe Epilepsy[J]. J Neurosci,2004, 24(39):8629-8639.
[18]  Naylor DE, Liu H, Wasterlain CG.Trafficking of GABA A Receptors, Loss of Inhibition, and a Mechanism for Pharmacoresistance in Status Epilepticus[J]. J Neurosci,2005, 25(34):7724-7733.

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