Empson R M, Amitai Y, Jefferys J G, Gutnick M J
Department of Physiology and Biophysics, St Mary's Hospital Medical School, Imperial College, London, U.K.
Neuroscience. 1993 Nov;57(2):235-9. doi: 10.1016/0306-4522(93)90058-n.
Focal injection of a minute quantity of tetanus toxin into the rat neocortex induces chronic epileptogenesis. Within a day, spontaneous and stimulus-evoked paroxysmal discharges appear in widespread regions of both hemispheres and this lasts for at least nine months. Tetanus toxin blocks transmitter release, apparently by catalysing the breakdown of synaptobrevin, a synaptic protein. It specifically binds to neuronal membranes but its potent epileptogenic properties have been ascribed to a higher affinity for inhibitory neurons. Following focal injection of tetanus toxin into the hippocampus a long-lasting epileptic syndrome also develops. During the early part of the syndrome GABA release is depressed in slices from the injected side, but not in slices from the contralateral, secondary focus. In the present experiments on neocortex, release of radiolabelled GABA was measured from primary and secondary epileptic foci induced by unilateral focal injection of tetanus toxin into the parietal cortex. By four weeks after the injection, no differences were detected in GABA release from any neocortical site in control or toxin-injected animals, despite the persistence of profound epileptic activity in slices from the latter. At earlier times (1.5 days) after the toxin injection, however, release was significantly depressed in both hemispheres. The results indicate that at first, the toxin induces focal neocortical epileptogenesis by directly impeding GABAergic synaptic transmission but that with time there is a recovery from this initial effect. We propose, as has also been suggested for other models, that the initial epileptogenesis leaves in its wake a long-lasting change in the local functional connectivity, such that the neocortex is rendered permanently epileptic.
向大鼠新皮层局部注射微量破伤风毒素会诱发慢性癫痫发生。在一天之内，双侧半球的广泛区域会出现自发和刺激诱发的阵发放电，这种情况会持续至少九个月。破伤风毒素显然通过催化突触小泡蛋白（一种突触蛋白）的分解来阻断神经递质释放。它特异性地结合神经元膜，但其强大的致癫痫特性被认为是对抑制性神经元具有更高的亲和力。向海马体局部注射破伤风毒素后也会出现持久的癫痫综合征。在综合征早期，注射侧切片中的GABA释放受到抑制，但对侧继发性病灶的切片中则没有。在目前关于新皮层的实验中，测量了通过向顶叶皮层单侧局部注射破伤风毒素诱导的原发性和继发性癫痫病灶中放射性标记的GABA释放。注射后四周，在对照动物或注射毒素的动物的任何新皮层部位，GABA释放均未检测到差异，尽管后者切片中仍存在严重的癫痫活动。然而，在毒素注射后的早期（1.5天），双侧半球的释放均显著降低。结果表明，起初，毒素通过直接阻碍GABA能突触传递诱导局部新皮层癫痫发生，但随着时间的推移，这种初始效应会恢复。我们提出，正如其他模型所表明的那样，初始癫痫发生会在局部功能连接中留下持久的变化，从而使新皮层永久癫痫化。
