Isoflurane Prevents Acquired Epilepsy in Rat Models of Temporal Lobe Epilepsy
Isoflurane Prevents Acquired Epilepsy in Rat Models of Temporal Lobe Epilepsy
复制标题
DOI：
10.1002/ana.24804
复制
发表时间：
2016-12-01
影响因子：
11.2
通讯作者：
Loescher, Wolfgang
中科院分区：
文献类型：
--
作者：
Bar-Klein, Guy;Klee, Rebecca;Loescher, Wolfgang
目的：获得性癫痫是各种脑损伤的破坏性长期风险，包括创伤，中风，感染和癫痫持续状态（SE）。对有风险的患者没有预防性治疗。由于癫痫发生的复杂变化，很可能需要多靶点方法来预防癫痫。我们报告新的临床前研究结果与异氟烷，发挥各种非麻醉作用，可能是相关的antiepileptogenesis.Methods：异氟烷的影响进行了研究，在两个大鼠模型SE诱导的癫痫：海马内红藻氨酸和全身给药对氧磷。在（红藻氨酸）或（对氧磷）诱导SE期间或之后给予异氟烷。磁共振成像用于评估血脑屏障（BBB）功能障碍。正电子发射断层扫描用于可视化神经炎症。长期皮质电图记录被用来监测自发性复发性癫痫发作。神经元损伤进行了评估histologic.Results：在异氟烷的情况下，自发性反复发作是常见的，在大多数大鼠在两种模型。当在红藻氨酸注射期间给予异氟烷时，SE的持续时间和严重程度不受影响，但只有少数大鼠发生自发性复发性癫痫发作。当对氧磷处理的大鼠在SE后暴露于异氟烷时，发现了类似的抗癫痫作用。此外，在后者的模型中，异氟烷防止血脑屏障功能障碍和神经退行性变，而异氟烷减少神经炎症的红藻氨酸model.Interpretation：鉴于异氟烷是一种广泛使用的挥发性麻醉剂，并用于吸入长期镇静在危重病人的风险发展癫痫，我们的研究结果持有一个有希望的潜力，成功地转化为临床。
Objective: Acquired epilepsy is a devastating long-term risk of various brain insults, including trauma, stroke, infections, and status epilepticus (SE). There is no preventive treatment for patients at risk. Attributable to the complex alterations involved in epileptogenesis, it is likely that multitargeted approaches are required for epilepsy prevention. We report novel preclinical findings with isoflurane, which exerts various nonanesthetic effects that may be relevant for antiepileptogenesis.Methods: The effects of isoflurane were investigated in two rat models of SE-induced epilepsy: intrahippocampal kainate and systemic administration of paraoxon. Isoflurane was either administered during (kainate) or after (paraoxon) induction of SE. Magnetic resonance imaging was used to assess blood-brain barrier (BBB) dysfunction. Positron emission tomography was used to visualize neuroinflammation. Long-term electrocorticographic recordings were used to monitor spontaneous recurrent seizures. Neuronal damage was assessed histologically.Results: In the absence of isoflurane, spontaneous recurrent seizures were common in the majority of rats in both models. When isoflurane was administered during kainate injection, duration and severity of SE were not affected, but only few rats developed spontaneous recurrent seizures. A similar antiepileptogenic effect was found when paraoxon-treated rats were exposed to isoflurane after SE. Moreover, in the latter model, isoflurane prevented BBB dysfunction and neurodegeneration, whereas isoflurane reduced neuroinflammation in the kainate model.Interpretation: Given that isoflurane is a widely used volatile anesthetic, and is used for inhalational long-term sedation in critically ill patients at risk to develop epilepsy, our findings hold a promising potential to be successfully translated into the clinic.