Prolonged infusion of tetrodotoxin does not block mossy fiber sprouting in pilocarpine-treated rats
Prolonged infusion of tetrodotoxin does not block mossy fiber sprouting in pilocarpine-treated rats
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DOI：
10.1111/j.0013-9580.2004.67103.x
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发表时间：
2004-05-01
期刊：
影响因子：
5.6
通讯作者：
Buckmaster, PS
中科院分区：
文献类型：
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作者：
Buckmaster, PS
目的：苔藓纤维发芽是颞叶癫痫患者和模型中常见的异常现象。苔藓纤维发芽在癫痫发生中的作用尚不清楚，它的阻断在实验上甚至可能在治疗上都是有用的。以前试图阻止苔藓纤维发芽的结果令人失望或有争议。在一些大脑区域，长期应用钠通道阻滞剂河豚毒素可以防止轴突萌发和创伤后癫痫的发生。本研究验证了长期局部注射河豚毒素可阻止致痫治疗后苔藓纤维发芽的假说。方法：用匹罗卡品诱导成年大鼠癫痫持续状态。在匹罗卡品治疗几小时到3天后，植入一个带有插管的泵，指向齿状回，以0.25MU1/h的速度单独输送10MU的河豚毒素或载体。这种方法阻止了海马区的局部脑电活动(Galvan等人。《神经科学杂志》2000；20：2904-16)。连续给药28天后，灌流固定剂，用体视学技术对大鼠海马区进行解剖学分析。结果：河豚毒素组大鼠海马区注射河豚毒素免疫细胞化学阳性，而赋形剂组大鼠海马区未见明显阳性反应。注射河豚毒素的海马区和注射赋形剂的海马区显示出相似程度的肺门神经元丢失。TIMM染色显示无论是河豚毒素注射、赋形剂注射，还是两者都注射，海马区均可见苔藓纤维发芽。结论：河豚毒素长时间注射并不能阻止苔藓纤维发芽。这一发现表明，在癫痫治疗后，钠通道介导的神经元活动不是苔藓纤维发芽所必需的。
Purpose: Mossy fiber sprouting is a common abnormality found in patients and models of temporal lobe epilepsy. The role of mossy fiber sprouting in epileptogenesis is unclear, and its blockade would be useful experimentally and perhaps therapeutically. Results from previous attempts to block mossy fiber sprouting have been disappointing or controversial. In some brain regions, prolonged application of the sodium channel blocker tetrodotoxin prevents axon sprouting and posttrauma epileptogenesis. The present study tested the hypothesis that prolonged, focal infusion of tetrodotoxin would block mossy fiber sprouting after an epileptogenic treatment.Methods: Adult rats were treated with pilocarpine to induce status epilepticus. Several hours to 3 days after pilocarpine treatment, a pump with a cannula directed toward the dentate gyrus was implanted to deliver 10 muM tetrodotoxin or vehicle alone at 0.25 mu1/h. This method blocks local EEG activity in the hippocampus (Galvan et al. J Neurosci 2000; 20:2904-16). After 28 days of continuous infusion, rats were perfused with fixative, and their hippocampi analyzed anatomically with stereologic techniques.Results: Tetrodotoxin infusion was verified immunocytochemically in tetrodotoxin-treated but not vehicle-treated hippocampi. Tetrodotoxin-infused and vehicle-infused hippocampi displayed similar levels of hilar neuron loss. The Timm stain revealed mossy fiber sprouting regardless of whether hippocampi were treated with tetrodotoxin infusion, vehicle infusion, or neither.Conclusions: Prolonged infusion of tetrodotoxin did not block mossy fiber sprouting. This finding suggests that sodium channel-mediated neuronal activity is not necessary for mossy fiber sprouting after an epileptogenic treatment.