Bragin A, Engel J, Wilson C L, Vizentin E, Mathern G W
Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.
Epilepsia. 1999 Sep;40(9):1210-21. doi: 10.1111/j.1528-1157.1999.tb00849.x.
Unilateral intrahippocampal injections of kainic acid (KA) in rats produce spontaneous recurrent limbic seizures and morphologic changes in hippocampus that resemble hippocampal sclerosis in patients with medically refractory mesial temporal lobe epilepsy (MTLE), that form of temporal lobe epilepsy (TLE) associated with hippocampal sclerosis. Interictal in vivo electrophysiologic studies have revealed high-frequency (250-500 Hz) oscillations, termed fast ripples (FRs). These oscillations may uniquely occur in or adjacent to the site of hippocampal KA injection, in areas that generate spontaneous seizures. Similar field potentials also have been demonstrated in the epileptogenic region of patients with TLE. We have now characterized ictal electrographic patterns in this rat model for comparison with those in human TLE and begun to evaluate the role of FRs in the transition to ictus in the KA-treated rat.
Rats received unilateral intrahippocampal injections of KA and, after the development of spontaneous seizures, were implanted with multiple fixed and moveable microelectrodes for single unit, field potential, and EEG recording. They were then monitored by using video-EEG telemetry for several weeks to capture and evaluate electrographic and behavioral seizure types. Results were correlated with Timm's stain demonstration of mossy fiber sprouting.
Low-voltage fast (LVF) and hypersynchronous electrographic ictal-onset patterns were seen in the KA-treated rat that resembled similar ictal-onset patterns in patients with TLE. Hypersynchronous, but not LVF, ictal discharges were associated with recurrent FRs. As in the human, hypersynchronous ictal onsets originated predominantly in hippocampus, whereas LVF ictal onsets more often involved extrahippocampal structures. LVF ictal onsets occurred during wakefulness or paradoxical sleep and were usually associated with motor behavior, whereas hypersynchronous ictal onsets occurred during slow-wave sleep or periods of immobility and were not associated with motor behavior unless there was transition to another ictal electrographic pattern. Mossy fiber sprouting did not correlate with the frequency of ictal EEG discharges exhibited by each rat but was greater in those rats that demonstrated frequent behavioral seizures.
The electrographic features of spontaneous seizures in the KA-treated rat resemble those of patients with medically refractory TLE with respect to EEG pattern and localization. Our data suggest that hypersynchronous ictal onsets represent epileptogenic disturbances in hippocampal circuits, whereas LVF ictal onsets may involve extrahippocampal areas having more direct connections to the motor system. Hypersynchronous seizures may involve the same neuronal mechanisms that generate interictal FRs.
在大鼠单侧海马内注射海藻酸（KA）可引发自发性反复性边缘叶癫痫发作，并导致海马出现形态学改变，类似于药物难治性内侧颞叶癫痫（MTLE）患者的海马硬化，MTLE是一种与海马硬化相关的颞叶癫痫（TLE）。发作间期的体内电生理研究揭示了高频（250 - 500Hz）振荡，即快速涟漪（FRs）。这些振荡可能仅在海马KA注射部位或其附近、产生自发性癫痫发作的区域出现。类似的场电位也已在TLE患者的致痫区域得到证实。我们现在已对该大鼠模型中的发作期脑电图模式进行了特征描述，以便与人类TLE的模式进行比较，并开始评估FRs在KA处理的大鼠向发作期转变中的作用。
给大鼠单侧海马内注射KA，在出现自发性癫痫发作后，植入多个固定和可移动的微电极，用于单单位、场电位和脑电图记录。然后使用视频脑电图遥测技术对它们进行数周监测，以捕捉和评估脑电图及行为性癫痫发作类型。结果与苔藓纤维发芽的Timm染色显示相关。
在KA处理的大鼠中观察到低电压快速（LVF）和超同步脑电图发作起始模式，类似于TLE患者的类似发作起始模式。超同步而非LVF发作期放电与反复出现的FRs相关。与人类一样，超同步发作起始主要起源于海马，而LVF发作起始更常涉及海马外结构。LVF发作起始发生在清醒或异相睡眠期间，通常与运动行为相关，而超同步发作起始发生在慢波睡眠或静止期，除非转变为另一种发作期脑电图模式，否则与运动行为无关。苔藓纤维发芽与每只大鼠发作期脑电图放电频率无关，但在那些表现出频繁行为性癫痫发作的大鼠中更为明显。
KA处理的大鼠自发性癫痫发作的脑电图特征在脑电图模式和定位方面类似于药物难治性TLE患者。我们的数据表明，超同步发作起始代表海马回路中的致痫性干扰，而LVF发作起始可能涉及与运动系统有更直接连接的海马外区域。超同步癫痫发作可能涉及与发作间期FRs产生相同的神经元机制。
