Target-specific catecholamine elevation induced by anticonvulsant thalamic deep brain stimulation.
Target-specific catecholamine elevation induced by anticonvulsant thalamic deep brain stimulation.
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抗惊厥丘脑深部脑刺激引起的目标特异性儿茶酚胺升高。
DOI：
10.1111/j.1528-1167.2005.49304.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Mirski,MarekA
中科院分区：
文献类型：
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作者：
Ziai,WendyC;Sherman,DavidL;Bhardwaj,Anish;Zhang,Ning;Keyl,PenelopeM;Mirski,MarekA
目的：丘脑前核（AN）深部脑刺激（DBS）可有效提高实验模型中的脑电图和阵挛发作阈值。关于 DBS 具有抗惊厥作用的具体特性，人们知之甚少。我们试图检验这样的假设：实验性癫痫发作和 AN DBS 的抗惊厥作用会改变 AN 的潜在区域神经化学，特别是促进血清素能系统对局部电刺激。方法：对氟烷麻醉的成年 Sprague-Dawley 雄性大鼠进行立体定向双极刺激钢电极和透析探针引导插管在 AN 和后丘脑 (PT) 的双边放置，并放置实验前 48 小时使用四个硬膜外 EEG 螺钉电极。刺激（AN DBS）和非刺激（NO DBS）动物（每组 n = 7）均接受静脉注射。戊四氮（PTZ，5.5 毫克/千克/分钟）。同时记录丘脑和皮质脑电图，并在 20 分钟内从 AN 和 PT 收集微透析样本。在 PTZ 输注前 40 分钟进行 AN 刺激（150 μA；0.1 ms 脉冲持续时间），并在 PTZ 输注期间继续进行。结果：与对照组相比，双侧 AN 刺激延迟了 EEG 癫痫发作：82 ± 8 与 58 ± 5 分钟（p = 0.02）。单独输注 PTZ 或与刺激一起输注，会导致 AN 和 PT 部位的去甲肾上腺素 (NE) 稳定增加，但多巴胺不会增加 (p < 0.001)。尽管细胞外血清素的测量水平非常低，但代谢物 5-羟基吲哚乙酸 (5-HIAA) 在刺激后和惊厥前输注 PTZ 期间在 AN 中选择性增加 (p < 0.001)，在第一次全身性癫痫发作后返回到基线。结论：这些数据表明 PTZ 和 DBS 共同增强丘脑核中 NE 的非选择性释放，同时特异性刺激 AN 局部血清素。基线时以及单独使用 STIM 或 PTZ 输注期间的低血清素水平可能表明血清素再摄取系统有效，其中 5-HIAA 可以作为血清素活性的替代标志物。 AN 特异性血清素能活性的调节可能对于改变 PTZ 癫痫阈值至关重要，并且是 AN DBS 功效的重要神经递质系统。
Purpose:Anterior thalamic nucleus (AN) deep brain stimulation (DBS) is effective in raising EEG and clonic seizure threshold in experimental models. Little is known about the specific properties of DBS that afford its anticonvulsant effect. We sought to test the hypothesis that experimental seizures and the anticonvulsant action of AN DBS alter the underlying regional neurochemistry of AN, specifically with facilitation of the serotonergic system to local electrical stimulation.Methods:Halothane‐anesthetized adult Sprague–Dawley male rats underwent stereotactically guided bilateral placement of bipolar stimulating steel electrodes and dialysis probes–guide cannulae in AN and posterior thalamus (PT), and placement of four epidural EEG screw electrodes 48 h before experiments. Both stimulated (AN DBS) and nonstimulated (NO DBS) animals (n = 7 per group) were infused with i.v. pentylenetetrazol (PTZ, 5.5 mg/kg/min). Simultaneous thalamic and cortical EEG were recorded, and microdialysis samples were collected from AN and PT in 20‐min epochs. AN stimulation was delivered (150 μA; 0.1‐ms pulse duration) 40 min before and continued during PTZ infusion.Results:Bilateral AN stimulation delayed the onset of EEG seizures compared with controls: 82 ± 8 vs. 58 ± 5 min (p = 0.02). PTZ infusion alone, or together with stimulation, resulted in a steady increase in norepinephrine (NE), but not dopamine, at AN and PT sites (p < 0.001). Although extracellular serotonin was measured at very low levels, the metabolite, 5‐hydroxyindoleacetic acid (5‐HIAA) increased selectively in AN after stimulation and during preconvulsant infusion of PTZ (p < 0.001), returning to baseline after the first generalized seizure.Conclusions:These data suggest that PTZ and DBS together enhance the nonselective release of NE in thalamic nuclei while specifically stimulating AN‐localized serotonin. Low serotonin levels at baseline and during STIM alone or PTZ infusion may indicate efficient reuptake systems for serotonin, with 5‐HIAA serving as a surrogate marker for serotonergic activity. Modulation of the AN‐specific serotonergic activity may be critical in altering PTZ seizure threshold and be an important neurotransmitter system underlying the efficacy of AN DBS.