Traub R D, Whittington M A, Buhl E H, LeBeau F E, Bibbig A, Boyd S, Cross H, Baldeweg T
Department of Pharmacology, University of Birmingham School of Medicine, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
Epilepsia. 2001 Feb;42(2):153-70. doi: 10.1046/j.1528-1157.2001.26900.x.
We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (> approximately 70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures.
Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon-axon gap junctions between principal neurons, as supported by recent experimental data.
Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30-70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included.
Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure-prone brain, but possibly also in normal brain. The anticonvulsant potential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered.
我们提出一个可通过实验和临床进行检验的假设，该假设关乎有时先于局灶性癫痫发作起始的极快速（>约70赫兹）脑电图振荡的起源。这些振荡很重要，因为它们可能在癫痫发作的起始过程中起因果作用。
从患有局灶性皮质发育异常和顽固性癫痫的儿童获取硬膜下脑电图记录。在大鼠海马切片中进行细胞内和细胞外记录，并诱导群体活动，如下：(a) 浴加四甲铵（一种细胞内碱化剂，可打开缝隙连接）；(b) 浴加卡巴胆碱，一种胆碱能激动剂；以及(c) 局部压力注射高渗钾溶液。进行了详细的网络模拟，以便更好地理解振荡背后的细胞机制。模拟的一个主要特征是纳入了主要神经元之间的轴突 - 轴突缝隙连接，这得到了近期实验数据的支持。
在癫痫发作前的儿童中发现了极快速振荡，而且在癫痫发作期间的阵发以及发作间期阵发上也有叠加。在切片实验中，之前在发作间期样阵发上已观察到极快速振荡；我们现在展示在癫痫样阵发之前、之间和之后都存在这种振荡。极快速振荡也叠加在由卡巴胆碱或高渗钾诱导的伽马（30 - 70赫兹）振荡上，并且在后一种情况下，当化学突触被阻断时，极快速振荡变得连续。当纳入轴突缝隙连接时，模拟重现了这些数据。
主要神经元之间的电耦合，可能是通过轴突缝隙连接，可能是癫痫易感性大脑中极快速群体振荡的基础，但在正常大脑中也可能如此。应考虑间隙连接阻滞剂（如用于治疗溃疡疾病的生胃酮）的抗惊厥潜力。
