Patel S, Millan M H, Meldrum B S
Department of Neurology, Institute of Psychiatry, De Crespigny Park, London.
Exp Neurol. 1988 Jul;101(1):63-74. doi: 10.1016/0014-4886(88)90065-9.
We have used limbic convulsions induced by systemic pilocarpine in rats combined with focal intracerebral injections concurrently to study the initiation and spread of seizure activity. Protection against pilocarpine-seizure development by antagonism of excitatory or facilitation of inhibitory neurotransmission at focal sites establishes the anatomical circuits involved in the propagation of seizures. The excitatory amino acid antagonist 2-amino-7-phosphonoheptanoate (APH, selective for the NMDA preferring glutamate receptor subtype) is potently anticonvulsant after bilateral focal injections into the habenula or mediodorsal thalamus. The dose of APH required to give sustained protection against pilocarpine-induced convulsions is 10 pmol for lateral habenula and 50 pmol for mediodorsal thalamus. The GABA agonist muscimol produces a similar sustained protection following focal injections (100 pmol/side) into either the lateral habenula or the mediodorsal thalamus. An overall decrease in the efferent neurotransmission of these two brain regions results in a strong anticonvulsant effect indicating their importance in modulating limbic seizure activity.
我们采用大鼠全身性毛果芸香碱诱发的边缘叶惊厥并同时进行局灶性脑内注射，以研究癫痫发作活动的起始和传播。通过在局灶部位拮抗兴奋性神经传递或促进抑制性神经传递来预防毛果芸香碱诱发的癫痫发作，可确定参与癫痫传播的解剖学回路。兴奋性氨基酸拮抗剂2-氨基-7-磷酸庚酸（APH，对优先选择NMDA的谷氨酸受体亚型具有选择性）在双侧局灶性注射到缰核或丘脑背内侧核后具有强大的抗惊厥作用。给予持续保护以抵抗毛果芸香碱诱发惊厥所需的APH剂量，外侧缰核为10皮摩尔，丘脑背内侧核为50皮摩尔。GABA激动剂蝇蕈醇在局灶性注射（每侧100皮摩尔）到外侧缰核或丘脑背内侧核后产生类似的持续保护作用。这两个脑区传出神经传递的总体减少导致强大的抗惊厥作用，表明它们在调节边缘叶癫痫活动中的重要性。
