Role of adenosine in the antiepileptic effects of deep brain stimulation.

Role of adenosine in the antiepileptic effects of deep brain stimulation.
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DOI:
10.3389/fncel.2014.00312
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发表时间:
2014
影响因子:
5.3
通讯作者:
Covolan L
Covolan L
中科院分区:
医学2区
文献类型:
--
作者:
Miranda MF;Hamani C;de Almeida AC;Amorim BO;Macedo CE;Fernandes MJ;Nobrega JN;Aarão MC;Madureira AP;Rodrigues AM;Andersen ML;Tufik S;Mello LE;Covolan L

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尽管丘脑前核(AN)脑深部电刺激(DBS)治疗癫痫的有效性,负责这种疗法的抗癫痫作用的机制仍然难以捉摸。由于腺苷在动物模型中调节神经元兴奋性和癫痫发作活动,我们假设这种核苷可能是AN DBS作用中涉及的底物之一。我们应用5天的刺激,使慢性癫痫大鼠匹鲁卡品注射和记录癫痫样活动在海马切片。我们发现,给予DBS的动物脑片海马兴奋性降低,不易发生发作活动。在活体动物中,通过微透析测量,AN DBS显著增加海马中的腺苷水平。DBS在体外的兴奋性降低被完全废除的动物预处理A1受体拮抗剂,并强烈增强A1受体激动剂。我们的结论是,DBS的一些抗癫痫作用可能是由腺苷介导的。
Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine.
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