Timofeeva O A, Peterson G M
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA.
Epilepsy Res. 1999 Feb;33(2-3):99-115. doi: 10.1016/s0920-1211(98)00078-3.
It has been shown that massed stimulation (MS) of the amygdala or hippocampus does not result in seizure progression but in the 'phenomenon of adaptation', whereas alternate day rapid kindling (ADRK) produces reliable kindling (Lothman, E.W., Williamson, J.M., 1994. Brain Res. 649, 71-84). The goal of the present experiment was to determine if the two different effects are due to differences in mossy fiber sprouting and/or different seizure and postictal spike propagation patterns. Nine rats underwent MS (66-70 stimulations separated by 5-min interstimulus interval), six were exposed to ADRK (12 stimulations/day, every 30 min, with 4 stimulus days, each separated by 1 stimulus-free day), five rats served as control. All rats had electrodes implanted bilaterally in dorsal and ventral hippocampi (VH) and 14 of them had additional electrodes in the piriform cortex. Animals were stimulated in the left VH at afterdischarge threshold. There was no potentiation in seizure response 4-7 weeks after MS. In contrast, ADRK produced not only kindling but also ongoing epileptogenesis resulting 4-7 weeks later in spontaneous seizures and development of a prolonged convulsive state in response to the initially subconvulsive stimulus. Epileptiform activity during MS was mostly restricted to VH, whereas during ADRK it spread widely among studied structures including piriform cortex. Afterdischarges during MS were elicited frequently but seizures did not progress beyond stage 2-3. During ADRK, afterdischarges were evoked less frequently but seizures reached stage 4-7 by the end of the 3rd and 4th stimulus days. The fully kindled state was not reached at this time, but epileptogenic changes continued to progress. Seven weeks after the initial stimulation, both groups demonstrated mossy fiber sprouting of similar intensity in VH. We suggest, (1) frequent but predominantly local hippocampal afterdischarges induce mossy fiber sprouting, but this is not sufficient to produce significant enhancement in seizure susceptibility, and (2) the involvement of extra-hippocampal structures, possibly piriform cortex, and formation of an aberrant hippocampal-para-hippocampal circuit is required to result in a condition of progressive epileptogenesis.
研究表明，对杏仁核或海马体进行密集刺激（MS）不会导致癫痫发作进展，而是会产生“适应现象”，而隔日快速点燃（ADRK）则会产生可靠的点燃效果（洛思曼，E.W.，威廉姆森，J.M.，1994年。《脑研究》649，71 - 84）。本实验的目的是确定这两种不同的效应是否归因于苔藓纤维发芽的差异和/或不同的癫痫发作及发作后棘波传播模式。九只大鼠接受了MS（66 - 70次刺激，刺激间隔为5分钟），六只大鼠接受了ADRK（每天12次刺激，每30分钟一次，共4个刺激日，每个刺激日之间间隔1个无刺激日），五只大鼠作为对照。所有大鼠双侧海马体背侧和腹侧（VH）均植入电极，其中14只大鼠在梨状皮质还额外植入了电极。动物在左VH以放电后阈值进行刺激。MS后4 - 7周癫痫发作反应无增强。相比之下，ADRK不仅产生了点燃，还导致了持续的癫痫发生，4 - 7周后出现自发性癫痫发作，并对最初的亚惊厥刺激产生了延长的惊厥状态。MS期间的癫痫样活动大多局限于VH，而ADRK期间它在包括梨状皮质在内的研究结构中广泛传播。MS期间放电后经常诱发，但癫痫发作未超过2 - 3期。ADRK期间，放电后诱发频率较低，但在第3和第4个刺激日结束时癫痫发作达到4 - 7期。此时尚未达到完全点燃状态，但致痫性变化继续进展。初始刺激7周后，两组在VH中均表现出相似强度的苔藓纤维发芽。我们认为，（1）频繁但主要局限于海马体的放电后诱发苔藓纤维发芽，但这不足以显著增强癫痫易感性，（2）需要海马体外结构（可能是梨状皮质）的参与以及异常海马 - 海马旁回路的形成才能导致进行性癫痫发生的状态。
