Following stroke, attenuation of detrimental inflammatory pathways might be a promising strategy to improve long-term outcome. In particular, cascades driven by pro-inflammatory chemokines interact with neurotransmitter systems such as the GABAergic system. This crosstalk might be of relevance for mechanisms of neuronal plasticity, however, detailed studies are lacking. The purpose of this study was to determine if treatment with 1,1′-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and partial allosteric agonist to CXCR7 (AMD3100) alone or in combination with C-X3-C chemokine receptor type 1 (CX3CR1) deficiency, affect the expression of GABA_A subunits and glutamate decarboxylase (GAD) isoforms. Heterozygous, CX3CR1-deficient mice and wild-type littermates were subjected to photothrombosis (PT). Treatment with AMD3100 (0.5 mg/kg twice daily i.p.) was administered starting from day 2 after induction of PT until day 14 after the insult. At this time point, GABA_A receptor subunits (α3, β3, δ), GAD65 and GAD67, and CXCR4 were analyzed from the peri-infarct tissue and homotypic brain regions of the contralateral hemisphere by quantitative real-time PCR and Western Blot. Fourteen days after PT, CX3CR1 deficiency resulted in a significant decrease of the three GABA_A receptor subunits in both the lesioned and the contralateral hemisphere compared to sham-operated mice. Treatment with AMD3100 promoted the down-regulation of GABA_A subunits and GAD67 in the ipsilateral peri-infarct area, while the β3 subunit and the GAD isoforms were up-regulated in homotypic regions of the contralateral cortex. Changes in GABA_A receptor subunits and GABA synthesis suggest that the CXCR4/7 and CX3CR1 signaling pathways are involved in the regulation of GABAergic neurotransmission in the post-ischemic brain.

中风后，减弱有害炎症通路可能是改善长期预后的有希望的策略。特别是，由促炎趋化因子驱动的级联与神经递质系统（如 GABA 能系统）相互作用。这种串扰可能与神经元可塑性机制有关，但是缺乏详细的研究。本研究的目的是确定是否用 1,1'-[1,4-苯双（亚甲基）]双[1,4,8,11-四氮杂环十四烷]（AMD3100）（一种 CXC 趋化因子受体类型的拮抗剂）进行治疗4 (CXCR4) 和 CXCR7 (AMD3100) 的部分变构激动剂单独或与 C-X3-C 趋化因子受体 1 型 (CX3CR1) 缺乏联合使用，影响 GABA _A的表达亚基和谷氨酸脱羧酶 (GAD) 异构体。杂合子、CX3CR1 缺陷小鼠和野生型同窝仔鼠接受光血栓形成 (PT)。从 PT 诱导后第 2 天开始，直至损伤后第 14 天，给予 AMD3100 (0.5 mg/kg，每天两次 ip) 治疗。此时，通过定量实时PCR和Western Blot从对侧半球的梗塞周围组织和同型脑区分析GABA _{A受体亚基（α3、β3、δ）、GAD65和GAD67以及CXCR4。}PT 后 14 天，与假手术小鼠相比，CX3CR1 缺乏导致受损半球和对侧半球中的三个 GABA _{A受体亚基显着减少。}AMD3100 治疗促进 GABA 的下调_A亚基和 GAD67 在同侧梗塞周围区域，而 β3 亚基和 GAD 同种型在对侧皮质的同型区域中上调。GABA _A受体亚基和 GABA 合成的变化表明 CXCR4/7 和 CX3CR1 信号通路参与了缺血后脑中 GABA 能神经传递的调节。