Costa Cinzia, Leone Giorgia, Saulle Emilia, Pisani Francesco, Bernardi Giorgio, Calabresi Paolo
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Tor Vergata, Rome, Italy.
Stroke. 2004 Feb;35(2):596-600. doi: 10.1161/01.STR.0000113691.32026.06. Epub 2004 Jan 15.
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.
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).
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.
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.
研究内源性γ-氨基丁酸（GABA）对体外缺血诱导的纹状体神经元不可逆电生理变化可能具有的神经保护作用。特别地，本研究的目的是表征两种增强GABA能传递的抗癫痫药物的神经保护作用，这两种药物分别是GABA转运体抑制剂噻加宾和GABA转氨酶不可逆抑制剂氨己烯酸。
从大鼠皮质-纹状体脑片标本中记录细胞外场电位。通过切换至不含葡萄糖并用氮气替代氧气的人工脑脊液溶液来诱导体外缺血。
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出现不可逆丧失。相反，噻加宾和氨己烯酸部分地预防了缺血诱导的场电位丧失。令人惊讶的是，GABA(A)和GABA(B)受体拮抗剂均阻断了这些效应。因此，仅当联合应用GABA(A)和GABA(B)受体激动剂时才能获得神经保护作用，而单独给予单一激动剂时则不能。
靶向GABA能传递的抗癫痫药物可通过提高内源性GABA水平并经由GABA(A)和GABA(B)受体的激活来发挥对缺血的神经保护作用。
