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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Targeting Seizure-Induced Neurogenesis in a Clinically Relevant Time Period Leads to Transient But Not Persistent Seizure Reduction
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Targeting Seizure-Induced Neurogenesis in a Clinically Relevant Time Period Leads to Transient But Not Persistent Seizure Reduction

机译：靶向诱导的神经发生在临床相关的时间段中导致瞬态但不持续的癫痫发作减少

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Mesial temporal lobe epilepsy (mTLE), the most common form of medically refractory epilepsy in adults, is usually associated with hippocampal pathophysiology. Using rodent models of mTLE, many studies including work from our laboratory have shown that new neurons born around the onset of severe acute seizures known as status epilepticus (SE) are crucial for the process of epileptogenesis and targeting seizure-induced neurogenesis either genetically or pharmacologically can impact the frequency of chronic seizures. However, these studies are limited in their clinical relevance as none of them determines the potential of blocking new neurons generated after the epileptogenic insult to alleviate the development of chronic seizures. Therefore, using a pilocarpine-induced SE model of mTLE in mice of either sex, we show that >4 weeks of continuous and concurrent ablation of seizure-induced neurogenesis after SE can reduce the formation of spontaneous recurrent seizures by 65%. We also found that blocking post-SE neurogenesis does not lead to long-term seizure reduction as the effect was observed only transiently for 10 d with >4 weeks of continuous and concurrent ablation of seizure-induced neurogenesis. Thus, these findings provide evidence that seizure-induced neurogenesis when adequately reduced in a clinically relevant time period has the potential to transiently suppress recurrent seizures, but additional mechanisms need to be targeted to permanently prevent epilepsy development.
机译：体育颞叶癫痫（咒语），成人中最常见的药物难治性癫痫形式，通常与海马病理生理学相关。使用粪便模型，许多研究包括我们实验室的工作，表明，围绕着名称癫痫发作的新神经元称为状态癫痫症（SE）对于癫痫发生和靶向诱导的神经发生的过程至关重要，无论是遗传还是药理学可以影响慢性癫痫发作的频率。然而，这些研究的临床相关性受到限制，因为它们中没有一个都决定了阻断癫痫肢体后产生的新神经元的潜力，以减轻慢性癫痫发作的发展。因此，在任何性别小鼠中使用潜水芸香碱诱导的粪型案例，我们展示了SE可以将自发性复发性癫痫发育的形成的连续和同时消融的癫痫发作的神经发生，以65％降低4周。我们还发现阻断后硒神经发生不会导致长期癫痫发作减少，因为仅在癫痫发作诱导的神经发生的连续和同时消融的瞬时观察到10d的效果。因此，这些发现提供了癫痫发作诱导的神经发生在临床相关的时间段中的癫痫发作的神经发生具有瞬时抑制复发性癫痫发作的潜力，但需要靶向永久性地预防癫痫发育的额外机制。

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