Department of Psychology, Behavior, Cognition and Neuroscience Program, American University, Washington DC, United States.
Department of Health Studies, American University, Washington DC, United States; Center for Behavioral Neuroscience, American University, Washington DC, United States.
Seizure. 2021 Oct;91:213-227. doi: 10.1016/j.seizure.2021.06.028. Epub 2021 Jun 29.
An imbalance between excitation and inhibition has been a longstanding proposed mechanism regarding ictogenesis and epileptogenesis. This imbalance is related to increased extracellular glutamate in the brain and/or reduction in GABA concentrations, leading to excitotoxicity, seizures, and cell death. This review aims to summarize the microdialysis and magnetic resonance spectroscopy (MRS) literature investigating glutamate and GABA concentrations in epilepsy patients, present limitations, and suggest future directions to help direct the search for novel epilepsy treatments. The majority of microdialysis studies demonstrated increased glutamate in epileptic regions either compared to control regions or to baseline levels; however, sample sizes were small, with some statistical comparisons missing. For the MRS research, two of six studies reported significant changes in glutamate levels compared to controls, though the results were mixed, with one reporting increased and the other reporting decreased glutamate levels. Eleven of 20 studies reported significant changes in Glx (glutamate + glutamine) or Glx ratios, with most reporting increased levels, except for a few epilepsy syndromes where reduced levels were reported. Few studies investigated GABA concentrations, with one microdialysis and four spectroscopy studies reporting increased GABA levels, and one study reporting decreased GABA in a different brain region. Based on this review, future research should account for medication use; include measurements of GABA, glutamate, and glutamine; use high-tesla strength MRI; and further evaluate the timing of microdialysis. Understanding the importance of brain glutamate and GABA levels in epilepsy may provide direction for future therapies and treatments.
兴奋与抑制失衡一直是关于癫痫发作和癫痫形成的一个长期提出的机制。这种失衡与大脑中细胞外谷氨酸的增加和/或 GABA 浓度的降低有关，导致兴奋性毒性、癫痫发作和细胞死亡。本综述旨在总结研究癫痫患者谷氨酸和 GABA 浓度的微透析和磁共振波谱（MRS）文献，提出局限性，并为寻找新的癫痫治疗方法提供未来的研究方向。大多数微透析研究表明，与对照区域或基线水平相比，癫痫区域的谷氨酸增加；然而，样本量较小，一些统计比较缺失。对于 MRS 研究，六项研究中有两项报告了与对照组相比谷氨酸水平的显著变化，尽管结果不一致，一项报告谷氨酸水平增加，另一项报告谷氨酸水平降低。20 项研究中有 11 项报告了 Glx（谷氨酸+谷氨酰胺）或 Glx 比值的显著变化，大多数报告谷氨酸水平升高，除了少数癫痫综合征报告谷氨酸水平降低。很少有研究调查 GABA 浓度，一项微透析和四项光谱研究报告 GABA 水平升高，一项研究报告不同脑区 GABA 水平降低。基于本综述，未来的研究应考虑药物使用；包括 GABA、谷氨酸和谷氨酰胺的测量；使用高场强 MRI；并进一步评估微透析的时间。了解癫痫中大脑谷氨酸和 GABA 水平的重要性可能为未来的治疗方法提供方向。
