Laboratório de Neurociência Experimental e Computacional, Universidade Federal de São João del-Rei São João del-Rei, Brazil.
Disciplina de Neurofisiologia, Universidade Federal de São Paulo São Paulo, Brazil ; Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health Toronto, Canada ; Division of Neurosurgery, Toronto Western Hospital, University of Toronto Toronto, Canada.
Front Cell Neurosci. 2014 Oct 2;8:312. doi: 10.3389/fncel.2014.00312. eCollection 2014.
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.
尽管前丘脑核（AN）深部脑刺激（DBS）在治疗癫痫方面非常有效，但这种治疗方法的抗癫痫作用机制仍难以捉摸。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参与 AN DBS 作用的底物之一。我们对通过匹罗卡品注射致慢性癫痫的大鼠施加 5 天的刺激，并在海马切片中记录癫痫样活动。我们发现，给予 DBS 的动物的切片显示海马兴奋性降低，并且不易发生癫痫发作活动。在活体动物中，通过微透析测量，AN DBS 显著增加了海马中的腺苷水平。在预先用 A1 受体拮抗剂处理的动物中，体外 DBS 的兴奋性降低完全被消除，并且被 A1 受体激动剂强烈增强。我们得出结论，DBS 的一些抗癫痫作用可能是通过腺苷介导的。
