Chatt A B, Ebersole J S
Brain Res. 1984 Mar 19;295(2):394-400. doi: 10.1016/0006-8993(84)90994-6.
Clinically, phenytoin is thought to be useful in controlling seizure activity by preventing it's spread from the focus to neighboring tissue. Experimentally, it has been suggested that phenytoin's principal action is no longer polysynaptic pathways with primary foci affected less than surrounding tissue. In this study, we present data confirming these basic experimental conclusions in foci induced in striate neocortical layer 4 of the cat. By using discrete penicillin microinjections strategically placed into this most penicillin-sensitive neocortical layer and recording simultaneously from several layers, we have been able to expand upon these conclusions by identifying this differential action at the interlaminar level. Epileptiform activity recorded from superficial laminae bordering layer 4, and into which layer 4's primary projections terminate, is suppressed preferentially by phenytoin. These superficial layers are also those that project into neighboring areas of the cat visual cortex. It would appear, then, that phenytoin begins protecting the cortex from seizure spread at the first synaptic termination into which this layer 4 primary focus projects. A discussion of the basic mechanisms of action that may be responsible for these results is also presented.
临床上,苯妥英钠被认为可通过阻止癫痫活动从病灶扩散至邻近组织来控制癫痫发作。实验表明,苯妥英钠的主要作用不再是多突触通路,原发性病灶受影响程度小于周围组织。在本研究中,我们提供的数据证实了在猫视皮层第4层诱发的病灶中的这些基本实验结论。通过将离散的青霉素微量注射剂有策略地注入这个对青霉素最敏感的新皮层层,并同时从几层进行记录,我们能够通过在层间水平识别这种差异作用来扩展这些结论。从与第4层相邻的浅层记录到的癫痫样活动,以及第4层的主要投射终止于此的浅层,优先受到苯妥英钠的抑制。这些浅层也是投射到猫视觉皮层邻近区域的层。那么,似乎苯妥英钠在第4层原发性病灶投射的第一个突触终末处就开始保护皮层免受癫痫扩散。本文还讨论了可能导致这些结果的基本作用机制。