Coactivation of GABAA and GABAB receptor results in neuroprotection during in vitro ischemia
Coactivation of GABAA and GABAB receptor results in neuroprotection during in vitro ischemia
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DOI：
10.1161/01.str.0000113691.32026.06
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发表时间：
2004-02-01
期刊：
影响因子：
8.3
通讯作者：
Calabresi, P
中科院分区：
文献类型：
--
作者：
Costa, C;Leone, G;Calabresi, P
背景和目的-研究了内源性γ-氨基丁酸（GABA）对纹状体神经元体外缺血引起的不可逆电生理变化的可能神经保护作用。特别是，这项研究的目的是表征的神经保护作用的2种抗癫痫药物增加GABA能的传输，如噻加宾，GABA转运抑制剂，和氨己烯酸，GABA transamine.Methods的不可逆抑制剂-细胞外场电位记录从大鼠皮质纹状体切片制备。体外缺血是通过切换到人工脑脊液溶液中，其中不含葡萄糖，用N-2代替氧气来实现的。结果在对照溶液中缺血10分钟后，观察到纹状体神经元记录的场电位的不可逆损失。相反，噻加宾和氨己烯酸部分防止缺血引起的场电位损失。令人惊讶的是，GABA（A）和GABA（B）受体拮抗剂都阻断了这些作用。因此，只有当GABA（A）和GABA（B）受体激动剂共同应用时，才能获得神经保护作用，而不是当单独给予单一激动剂时。结论-靶向GABA能传递的抗癫痫药物可以通过增加内源性GABA水平和通过激活GABA（A）和GABA（B）受体来对缺血发挥神经保护作用。
Background and Purpose - The possible neuroprotective effect of endogenous gamma-aminobutyric acid ( GABA) on the irreversible electrophysiological changes induced by in vitro ischemia on striatal neurons was investigated. In particular, the aim of the study was the characterization of the neuroprotective action of 2 antiepileptic drugs increasing GABAergic transmission such as tiagabine, a GABA transporter inhibitor, and vigabatrin, an irreversible inhibitor of GABA transaminase.Methods - Extracellular field potential recordings were obtained from rat corticostriatal slice preparations. In vitro ischemia was delivered by switching to an artificial cerebrospinal fluid solution in which glucose was omitted and oxygen was replaced with N-2.Results - An irreversible loss of the field potentials recorded from striatal neurons was observed after 10 minutes of ischemia in control solution. Conversely, tiagabine and vigabatrin partially prevented the ischemia-induced field potential loss. Surprisingly, both GABA(A) and GABA(B) receptor antagonists blocked these effects. Accordingly, neuroprotection could be obtained only when GABA(A) and GABA(B) receptor agonists were coapplied, but not when a single agonist was given in isolation.Conclusions - Antiepileptic drugs targeting GABAergic transmission can exert neuroprotective effects against ischemia by increasing endogenous GABA levels and via the activation of both GABA(A) and GABA(B) receptors.