Role of the fastigial nucleus in generalized seizures as demonstrated by GABA agonist microinjections.

Role of the fastigial nucleus in generalized seizures as demonstrated by GABA agonist microinjections.
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GABA 激动剂显微注射证明顶核在全身性癫痫发作中的作用。

DOI:
10.1111/j.1528-1157.1993.tb02121.x
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发表时间:
1993
期刊:
影响因子:
5.6
通讯作者:
Turner,GM
Turner,GM
中科院分区:
医学1区
文献类型:
--
作者:
Miller,JW;Gray,BC;Turner,GM

文献摘要

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在癫痫发作期间,小脑在电和代谢方面是活跃的。大量研究也表明,小脑电刺激和小脑皮质或核团损毁影响惊厥阈值,但存在显著的矛盾,即使在使用相同种类和相似的惊厥类型的调查和实验操作中也观察到不同的效果。离散的脑内微量注射神经活性物质已被用于表征其他脑区控制癫痫发作的方式,但尚未应用于小脑系统。这种方法具有优势,因为影响仅限于特定的感受器和备用的传递轴突;实验变量也可以简单地指定和重现。我们使用这种方法来表征小脑NU Clei在癫痫发作中的作用,并确定不同药物在不同剂量下是否可以重现观察到的效果。比较不同剂量GABA激动剂哌啶-4-磺酸和GABA激动剂(−)巴氯芬(Bf)对双侧小脑顶(内侧)核微量注射的影响。在注射后不久,这些动物就出现了共济失调。4min后,定时连续静脉注射诱发癫痫发作。补肾活血碱(BIC)输液。两种GABA激动剂均显著降低肌阵挛、阵挛和紧张性运动阈值。背侧或前侧注射和双侧齿状(外侧)核注射对癫痫发作几乎没有影响。这些结果表明,小脑系统确实控制癫痫发作,但不支持早期的概念,即小脑刺激和全身性苯妥英钠通过抑制继发于pur kinje细胞激活的小脑核来阻断癫痫发作。
The cerebellum is electrically and metaboli cally active during seizures. Numerous studies have also shown that cerebellar electrical stimulation and lesions of the cerebellar cortex or nuclei influence seizure thresh old, but there are significant contradictions, with different effects observed even in investigations using the same species and similar seizure types and experimental ma nipulations. Discrete intracerebral microinjection of neu roactive agents has been used to characterize the way in which other brain regions control seizures, but has not been applied to the cerebellar systems. This approach has advantages because effects are restricted to specific re ceptors and spare passing axons; experimental variables also can be simply specified and reproduced. We used this method to characterize the role of the cerebellar nu clei in seizures and to determine if observed effects could be reproduced with different agents at different doses. Effects of bilateral control microinjections in the fastigial (medial) cerebellar nucleus were compared with different doses of the GABAAagonist piperidine‐4‐sulfonic acid and the GABABagonist (−)baclofen (Bf). Soon after in jection, the animals were ataxic. After 4 min, seizures were induced by timed continuous intravenous (i.v.) bicu culline (BIC) infusion. Both GABA agonists produced significant reductions in myoclonic, clonic, and tonic sei zure thresholds. Injections just dorsal or anterior to this nucleus and bilateral dentate (lateral) nucleus injections had little effect on seizures. These results demonstrate that the cerebellar system does control seizures, but does not provide support for the early concept that cerebellar stimulation and systemic phenytoin block seizures through inhibition of cerebellar nuclei secondary to Pur kinje cell activation.