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破伤风毒素作为研究癫痫的一种工具。

Tetanus toxin as a tool for studying epilepsy.

作者信息

Mellanby J, Hawkins C, Mellanby H, Rawlins J N, Impey M E

出版信息

J Physiol (Paris). 1984;79(4):207-15.

PMID:6530666
Abstract

The use of tetanus toxin, injected into the hippocampus of the rat, to produce an "animal model" of chronic limbic epilepsy is described. This model has yielded information complementary to that derived from other animal models and has several important advantages: while it involves spontaneous seizures, it occurs without gross damage to the brain ; it is eventually reversible in terms of fits and the overall reappearance of the EEG. It can therefore be used to look both at the effects of ongoing epilepsy and also at the long-term changes in brain function induced by previous epilepsy. Evidence is presented that the toxin probably remains localised at the site of injection. The information which has so far been obtained with this model on the relation between epilepsy and abnormal behaviour is summarised. In particular, it appears that the epilepsy produces long-term deficits in the animals' ability to learn and remember of a sort which suggest that an enduring malfunction has been induced in the hippocampus. The significance of the findings for clinical research and for future investigation of the nature of epilepsy are described. It is emphasised that the neurotoxins may be usefully exploited not only for investigating the molecular basis of neuronal mechanisms but also for inducing long-lasting plastic changes in integrated brain function.

摘要

本文描述了通过向大鼠海马体注射破伤风毒素来建立慢性边缘性癫痫“动物模型”的方法。该模型所提供的信息与其他动物模型互补,且具有几个重要优点:虽然它会引发自发性癫痫发作,但不会对大脑造成严重损伤;就癫痫发作和脑电图的整体恢复而言,最终是可逆的。因此,它既可以用于研究持续性癫痫的影响,也可以用于研究先前癫痫发作所诱发的大脑功能的长期变化。有证据表明,毒素可能局限于注射部位。总结了迄今为止利用该模型获得的关于癫痫与异常行为之间关系的信息。特别是,癫痫似乎会导致动物学习和记忆能力出现长期缺陷,这表明海马体已诱发了持久性功能障碍。阐述了这些发现对临床研究以及未来癫痫本质研究的意义。强调了神经毒素不仅可用于研究神经元机制的分子基础,还可用于诱导整合脑功能的持久可塑性变化。

相似文献

1
Tetanus toxin as a tool for studying epilepsy.破伤风毒素作为研究癫痫的一种工具。
J Physiol (Paris). 1984;79(4):207-15.
2
Do fits really beget fits? The effect of previous epileptic activity on the subsequent induction of the tetanus toxin model of limbic epilepsy in the rat.癫痫发作真的会引发癫痫发作吗?大鼠先前癫痫活动对随后边缘叶癫痫破伤风毒素模型诱导的影响。
Neurobiol Dis. 2001 Aug;8(4):679-91. doi: 10.1006/nbdi.2001.0417.
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Characterization of the tetanus toxin model of refractory focal neocortical epilepsy in the rat.大鼠难治性局灶性新皮质癫痫破伤风毒素模型的特征描述。
Epilepsia. 2005 Feb;46(2):179-87. doi: 10.1111/j.0013-9580.2005.26004.x.
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Investigation of the neuronal aggregate generating seizures in the rat tetanus toxin model of epilepsy.在大鼠破伤风毒素癫痫模型中对引发癫痫发作的神经元聚集体的研究。
J Neurophysiol. 2002 Dec;88(6):2919-27. doi: 10.1152/jn.00211.2002.
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Basic research in epilepsy and aging.癫痫与衰老的基础研究
Epilepsy Res. 2006 Jan;68 Suppl 1:S21-37. doi: 10.1016/j.eplepsyres.2005.07.014. Epub 2005 Dec 27.
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Effects of stereotactic radiosurgery on an animal model of hippocampal epilepsy.立体定向放射外科对海马癫痫动物模型的影响。
Neurosurgery. 2000 Jan;46(1):157-65; discussion 165-8.
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Chronic epileptic foci induced by intracranial tetanus toxin.
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Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus.颞叶癫痫小鼠模型中的癫痫发生和慢性癫痫发作与对侧海马中不同的脑电图模式和选择性神经化学改变有关。
Exp Neurol. 2005 Jul;194(1):76-90. doi: 10.1016/j.expneurol.2005.01.029.
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Proechimys guyannensis: an animal model of resistance to epilepsy.圭亚那稻鼠:一种抗癫痫动物模型。
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10
Antiepileptic effect of gap-junction blockers in a rat model of refractory focal cortical epilepsy.缝隙连接阻滞剂在难治性局灶性皮质癫痫大鼠模型中的抗癫痫作用
Epilepsia. 2006 Jul;47(7):1169-75. doi: 10.1111/j.1528-1167.2006.00540.x.

引用本文的文献

1
Modeling the Interictal Epileptic State for Therapeutic Development with Tetanus Toxin.利用破伤风毒素模拟发作间期癫痫状态以促进治疗开发
Brain Sci. 2024 Jun 25;14(7):634. doi: 10.3390/brainsci14070634.
2
The Molecular Basis of Toxins' Interactions with Intracellular Signaling via Discrete Portals.毒素通过离散通道与细胞内信号传导相互作用的分子基础。
Toxins (Basel). 2017 Mar 16;9(3):107. doi: 10.3390/toxins9030107.
3
Optogenetics and epilepsy: past, present and future.光遗传学与癫痫:过去、现在和未来。
Epilepsy Curr. 2015 Jan-Feb;15(1):34-8. doi: 10.5698/1535-7597-15.1.34.
4
A comparison of the efficacy of carbamazepine and the novel anti-epileptic drug levetiracetam in the tetanus toxin model of focal complex partial epilepsy.卡马西平与新型抗癫痫药物左乙拉西坦在局灶性复杂部分性癫痫破伤风毒素模型中的疗效比较。
Br J Pharmacol. 2002 Mar;135(6):1425-34. doi: 10.1038/sj.bjp.0704606.
5
Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses.破伤风毒素与肉毒杆菌神经毒素:作用机制及治疗用途
Philos Trans R Soc Lond B Biol Sci. 1999 Feb 28;354(1381):259-68. doi: 10.1098/rstb.1999.0377.
6
Chronic focal epilepsy induced by intracerebral tetanus toxin.脑内破伤风毒素诱发的慢性局灶性癫痫
Ital J Neurol Sci. 1995 Feb-Mar;16(1-2):27-32. doi: 10.1007/BF02229071.
7
Experimental models of chronic focal epilepsy: a critical review of four models.慢性局灶性癫痫的实验模型:四种模型的批判性综述
Yale J Biol Med. 1987 May-Jun;60(3):255-72.
8
Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc.破伤风毒素是一种锌蛋白,其对神经递质释放和蛋白酶活性的抑制作用依赖于锌。
EMBO J. 1992 Oct;11(10):3577-83. doi: 10.1002/j.1460-2075.1992.tb05441.x.