Objective

Pharmacological inhibition of GABAergic synapses could represent a potent neuromodulation strategy to activate hippocampal neurons and increase neurotrophic factor gene expression, thus exerting a beneficial effect on post-stroke cognitive impairment (PSCI). The objective of this study was to assess the effects of low-level inhibition of GABAergic synapses on hippocampal gene expressions related to neuroplasticity using the middle cerebral artery occlusion surgery (MCAO) ischemic stroke rat model.

Methods

The animals were randomly assigned to three experimental groups—(1) a sham operated group (SHAM), (2) a control group (CON), and (3) a bicuculline group (BIC). MCAO was performed in the CON and BIC groups. A non-epileptic dose of bicuculline (0.25 mg/kg) was intraperitoneally administered every day for two weeks, starting three days after surgery, to the rats in the BIC group. The mRNA expression of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), in relation to neurotrophic intracellular signal, p75, in relation to apoptosis, and synaptophysin (SYP) and PSD-95, synaptic markers, were assessed in the hippocampus ipsilateral to the ischemic site.

Results

MCAO increased the gene expression of TrkB. Furthermore, MCAO plus bicuculline administration increased the expression ratio of TrkB to p75 and SYP gene expression.

Conclusion

Therefore, this study showed that administration of bicuculline after stroke beneficially modulated the expression of crucial genes for neuroplasticity, including BDNF receptors and SYP, in the ipsilateral hippocampus, suggesting that low-level inhibition of GABAergic synapses could lead to beneficial neuromodulation in the hippocampus after stroke.

中文翻译：

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GABA能突触的低水平抑制增强缺血性中风后海马神经元可塑性的关键基因表达。

目的

GABA能突触的药理抑制作用可能代表一种有效的神经调节策略，以激活海马神经元并增加神经营养因子基因的表达，从而对中风后认知障碍（PSCI）发挥有益作用。这项研究的目的是评估使用中脑动脉闭塞手术（MCAO）缺血性中风大鼠模型对GABA能突触的低水平抑制对与神经可塑性相关的海马基因表达的影响。

方法

将动物随机分为三个实验组-（1）假手术组（SHAM），（2）对照组（CON），和（3）双骨动物组（BIC）。MCAO在CON和BIC组中进行。从手术后三天开始，每天两次腹膜内注射非癫痫剂量的比库林（0.25 mg / kg）给BIC组的大鼠。脑源性神经营养因子（BDNF），原肌球蛋白相关激酶B（TrkB）与神经营养性细胞内信号p75有关（与凋亡有关）以及突触素（SYP）和PSD-95（mRNA）的mRNA表达为突触标记。在缺血部位同侧海马中评估。

结果

MCAO增加了TrkB的基因表达。此外，MCAO加双小分子给药可增加TrkB与p75和SYP基因表达的比率。

结论

因此，这项研究表明，中风后双小分子的给药可有效调节同侧海马中神经可塑性的关键基因（包括BDNF受体和SYP）的表达，这表明对GABA能突触的低水平抑制可能导致海马后GABA能突触的有益神经调节。中风。