Gamma-aminobutyric acid (GABA) changes in the hippocampus and anterior cingulate cortex in patients with temporal lobe epilepsy

Gamma-aminobutyric acid (GABA) changes in the hippocampus and anterior cingulate cortex in patients with temporal lobe epilepsy
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DOI:
10.1016/j.yebeh.2020.107683
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发表时间:
2021-02-01
影响因子:
2.6
通讯作者:
Yin, Jianzhong
Yin, Jianzhong
中科院分区:
医学3区
文献类型:
--
作者:
He, Che;Liu, Pei;Yin, Jianzhong

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目的:应用定量磁共振波谱(MRS)技术,探讨正常对照组和颞叶癫痫(TLE)患者双侧海马和前扣带皮层(ACC)γ-氨基丁酸(GABA)水平的变化及其与临床症状的相关性。N-乙酰天冬氨酸(NAA),采用定量Meshcher-1法测定40例TLE患者和26例健康对照者双侧海马和ACC内肌酸(Cr)、胆碱(Cho)和GABA(GABA)的含量。Garwood点分辨光谱法(MEGA-PRESS)。比较NC组和TLE组的NAA/(Cho + Cr)和GABA/Cr比值。还对TLE患者的偏侧性(左侧TLE、右侧TLE和不确定)、短(10年)临床癫痫发作史(CSH)、低(≥ 1次/月)癫痫发作频率(SF)、伴和不伴认知功能障碍(CI)以及抗癫痫药物治疗亚组进行了比较。结果:TLE患者双侧海马GABA/Cr比值明显降低,与对照组比较差异有统计学意义(P < 0. 05(左:P = 0.028,右:TLE患者右侧海马NAA/(Cho + Cr)比值较NC降低(P = 0.004)。双侧海马NAA/(Cho + Cr)比值在CSH时呈一致性下降趋势,仅在RH时有显著性差异。海马和ACC区GABA的变化在不同病程阶段并不一致。在双侧海马,短暂发作史(≥ 10年)的TLE患者GABA/Cr比值降低,但与NC无差异。而ACC中,脑梗死组GABA/Cr比值较NC组显著降低(P= 0.015)。进一步分析发现,与无认知功能损害(NOCI)组相比,TLE伴CI组的灰质体积(GMV)和脑实质总体积(PBV)明显萎缩,ACC的GABA/Cr比值降低,而双侧海马的GABA/Cr比值升高。GABA/Cr比值较NAA/(Cho + Cr)比值更能反映TLE患者代谢物的动态变化。重要的是,海马和ACC区域的GABA变化在疾病的不同阶段并不一致。双侧海马GABA/Cr比值早期降低,但随后恢复正常。ACC内GABA/Cr比值降低可能提示TLE患者大脑皮质受累较多,CI发生率较高。(C)2020爱思唯尔公司All rights reserved.
Purpose: To explore the changes of gamma-aminobutyric acid (GABA) levels in the bilateral hippocampus and anterior cingulate cortex (ACC) of healthy control subjects and patients with temporal lobe epilepsy (TLE) and the correlation of GABA levels with the clinical symptoms by quantitative magnetic resonance spectroscopy (MRS).Methods: N-acetylaspartate (NAA), creatine (Cr) as well as choline (Cho) and GABA levels in the bilateral hippocampus and ACC were measured in 40 patients with TLE and 26 healthy control (NC) subjects with quantitative Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS). The NAA/(Cho + Cr) and GABA/Cr ratios were compared between the NC and TLE groups. Comparisons were also made between the subgroups with lateralization (left TLE, right TLE and uncertain), short (10 years) clinical seizure history (CSH), low (= 1/month) seizure frequency (SF), with and without cognitive impairment (CI) in the patients with TLE, and by antiepileptic medications. Further analyses of the clinical information and metabolite ratios between the patients with TLE with and without CI were preformed.Results: The GABA/Cr ratio was significantly decreased in the bilateral hippocampus (left: P = 0.028, right: P= 0.035), while the NAA/(Cho + Cr) ratio was decreased only in the right hippocampus (RH) (P = 0.004) in patients with TLE compared with that of the NCs. Whereas the NAA/(Cho + Cr) ratio showed a consistent decreasing trend in bilateral hippocampus during the CSH, it only showed a significant difference in the RH. The GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased in the short seizure history (= 10 years) patients with TLE showed no difference with the NCs. However, in the ACC, the GABA/Cr ratio of the CI group was significantly decreased compared with that of NCs (P= 0.015). Further analysis showed that the patients with TLE with CI had obvious atrophy of the gray matter volume (GMV) and total parenchymal brain volume (PBV); GABA/Cr ratio was decreased in ACC, but increased in bilateral hippocampus compared with that of the no cognitive impairment (NOCI) group.Conclusion: The GABA/Cr ratio was more valuable than the NAA/(Cho + Cr) ratio in evaluating the dynamic metabolite changes in patients with TLE. Importantly, the GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased at the early stage, but recovered to normal levels later. The decreased GABA/Cr ratio in the ACC might indicate more cerebral cortex was involved, resulting in more CI in patients with TLE. (C) 2020 Elsevier Inc. All rights reserved.