电生理皮质兴奋性指标在精神障碍诊疗中的价值

精神疾病病因机制复杂,且具有易复发、致残率高等特点,多存在脑皮质活动的兴奋性或抑制性失常。发展无创、在体、定量检测精神疾病患者大脑皮质活动的客观指标,对深入探索精神疾病的发病机制和辅助临床诊断准确性提高至关重要。基于经颅磁刺激这一新兴的无创神经调控技术,联合神经电生理检测技术的日益成熟,提供了多项大脑皮质兴奋性和抑制性客观指标。本文概述经颅磁技术评估精神疾病大脑皮质活动的技术进展,并分别阐述其在精神疾病皮质活动评估和治疗疗效预测中的研究进展。

Pathological Networks Involving Dysmorphic Neurons in Type ⅡFocal Cortical Dysplasia

Focal cortical dysplasia(FCD)is one of the most common causes of drug-resistant epilepsy.Dysmorphic neurons are the major histopathological feature of typeⅡFCD,but their role in seizure genesis in FCD is unclear.Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients.Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in typeⅡFCD,including an enlarged soma,aberrant dendritic arbors,increased current injection for rheobase action potential firing,and reduced action potential firing frequency.Intriguingly,the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na^(+)-K^(+)-Cl^(−)cotransporter.In addition,we found a depolarizing shift of the GABA reversal potential in the CamKⅡ-cre::PTENflox/flox mouse model of drug-resistant epilepsy,suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons.Thus,imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in typeⅡFCD.

感觉运动训练联合皮层刺激对创伤性脑损伤大鼠平衡失调的改善作用

[目的]观察感觉运动训练联合皮层刺激对创伤性脑损伤大鼠平衡失调的改善作用。[方法]取SD大鼠100只,随机留取20只设为假手术组,其余80只建立创伤性脑损伤大鼠模型,将建模成功的72只大鼠随机分为模型组、感觉运动训练组、皮层刺激组和联合组,每组各18只。建模成功后,感觉运动训练组进行运动训练,皮层刺激组给予电刺激,联合组在每次给予电刺激后进行运动训练,干预时间均为4周;模型组和假手术组不进行任何干预。干预4周时,以平衡木测验评估各组大鼠的平衡功能,苏木素-伊红(hematoxylin-eosin,HE)染色进行伤侧海马区脑组织病理学检查,酶活性试剂盒测定伤侧大脑皮质中的脂质过氧化物丙二醛(malondialdehyde,MDA)的含量及超氧化物歧化酶(superoxide dismutase,SOD)活性,实时荧光定量聚合酶链式反应(Real-time quantitative-polymerase chain reaction,RT-qPCR)及Western blot检测伤侧大脑皮质中核因子-κB抑制因子激酶2(inhibitor of nuclear factor-κB kinase 2,IKK2)、核因子-κB(nuclear factor-κB,NF-κB)p65、NF-κB p50 mRNA和蛋白及磷酸化NF-κB p65(NF-κB phosphatedp65,NF-κB p-p65)、磷酸化NF-κB p50(NF-κB phosphated-p50,NF-κB p-p50)蛋白相对表达量。[结果]与模型组比较,感觉运动训练组、皮层刺激组、联合组大鼠通过平衡木时间均缩短,但仍长于假手术组(P<0.01);与感觉运动训练组及皮层刺激组比较,联合组大鼠通过平衡木时间缩短(P<0.01)。HE染色显示,假手术组海马区脑组织细胞排列规则,核膜完整;模型组细胞排列松散,细胞出现明显坏死,核膜破裂;感觉运动训练组、皮层刺激组及联合组上述病理变化均减轻,且联合组减轻最为明显。与模型组比较,感觉运动训练组、皮层刺激组、联合组SOD活性增加,但仍低于假手术组(P<0.05);与感觉运动训练组和皮层刺激组比较,联合组SOD活性增加(P<0.05)。与模型组比较,感觉运动训练组、皮层刺激组、联合组MDA含量、IKK2 mRNA和蛋白相对表达量及NF-κB p-p65/NF-κB p65、NF-κB p-p50/NF-κB p50降低,但仍高于假手术组(P<0.05);与感觉运动训练组和皮层刺激组比较,联合组MDA含量、IKK2 mRNA和蛋白相对表达量及NF-κB p-p65/NF-κB p65、NF-κB p-p50/NF-κB p50降低(P<0.05)。[结论]感觉运动训练联合皮层刺激对创伤性脑损伤大鼠的平衡失调具有改善作用,可能是通过抑制IKK2/NF-κB信号通路发挥作用。