Ralph N. Adams Institute for Bioanalytical Chemistry and Department of Chemistry, University of Kansas, Lawrence, KS 66047, United States.
Higuchi Biosciences Center and Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66047, United States.
Brain Res. 2019 Nov 1;1722:146360. doi: 10.1016/j.brainres.2019.146360. Epub 2019 Aug 1.
The objective of this study was to develop an in vivo model for locally induced epilepsy. Epilepsy is a prominent neurological disorder that affects millions of people worldwide. Patients may experience either global seizures, affecting the entire brain, or focal seizures, affecting only one brain region. The majority of epileptic patients experience focal seizures but they go undiagnosed because such seizures can be difficult to detect. To better understand the effects of focal epilepsy on the neurochemistry of a brain region with high seizure diathesis, an animal model for locally induced seizures in the hippocampus was developed. In this model, two seizure events were chemically induced by administering the epileptogenic agent, 3-mercaptopropionic acid (3-MPA), to the hippocampus to disturb the balance between excitatory and inhibitory neurotransmitters in the brain. Microdialysis was used for local delivery of 3-MPA as well as for collection of dialysate for neurochemical analyses. Two periods of seizures separated by varying inter-seizure recovery times were employed, and changes in the release of the excitatory transmitter, glutamate, were measured. Significant differences in glutamate release were observed between the first and second seizure episodes. Diminished glutamate biosynthesis, enhanced glutamate re-uptake, and/or neuronal death were considered possible causes of the attenuated glutamate release during the second seizure episode. Biochemical measurements were indicative that a combination of these factors led to the attenuation in glutamate release.
本研究的目的是建立一种局部诱导癫痫的体内模型。癫痫是一种影响全球数百万人的突出神经障碍。患者可能经历全身性发作，影响整个大脑，或局灶性发作，仅影响一个大脑区域。大多数癫痫患者经历局灶性发作，但由于这些发作难以检测，因此未被诊断出来。为了更好地了解局灶性癫痫对具有高发作倾向的脑区神经化学的影响，开发了一种在海马体中局部诱导发作的动物模型。在该模型中，通过向海马体施用致痫剂 3-巯基丙酸（3-MPA）来化学诱导两次发作事件，从而扰乱大脑中兴奋性和抑制性神经递质之间的平衡。微透析用于局部输送 3-MPA 以及收集用于神经化学分析的透析液。使用两种发作期，其间间隔不同的发作后恢复期，并测量释放的兴奋性递质谷氨酸的变化。在第一次和第二次发作事件之间观察到谷氨酸释放的显著差异。谷氨酸生物合成减少、谷氨酸再摄取增强和/或神经元死亡被认为是第二次发作期间谷氨酸释放减弱的可能原因。生化测量表明，这些因素的组合导致了谷氨酸释放的减弱。
