OBJECTIVE Birth asphyxia (BA) is often associated with seizures that may exacerbate the ensuing hypoxic-ischemic encephalopathy. In rodent models of BA, exposure to hypoxia is used to evoke seizures, that commence already during the insult. This is in stark contrast to clinical BA, in which seizures are typically seen upon recovery. Here, we introduce a term-equivalent rat model of BA, in which seizures are triggered after exposure to asphyxia. METHODS Postnatal day 11-12 male rat pups were exposed to steady asphyxia (15 min; air containing 5% O2 + 20% CO2 ) or to intermittent asphyxia (30 min; three 5 + 5-min cycles of 9% and 5% O2 at 20% CO2 ). Cortical activity and electrographic seizures were recorded in freely behaving animals. Simultaneous electrode measurements of intracortical pH, Po2 , and local field potentials (LFPs) were made under urethane anesthesia. RESULTS Both protocols decreased blood pH to <7.0 and brain pH from 7.3 to 6.7 and led to a fall in base excess by 20 mmol·L-1 . Electrographic seizures with convulsions spanning the entire Racine scale were triggered after intermittent but not steady asphyxia. In the presence of 20% CO2 , brain Po2 was only transiently affected by 9% ambient O2 but fell below detection level during the steps to 5% O2 , and LFP activity was nearly abolished. Post-asphyxia seizures were strongly suppressed when brain pH recovery was slowed down by 5% CO2 . SIGNIFICANCE The rate of brain pH recovery has a strong influence on post-asphyxia seizure propensity. The recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which leads to seizures only after the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our best knowledge the first one in which, consistent with clinical BA, behavioral and electrographic seizures are triggered after and not during the BA-mimicking insult.

中文翻译：

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经生理验证的足月出生窒息大鼠模型，在脑缺氧后而不是脑缺氧期间发生癫痫发作


目的 出生窒息（BA）通常与癫痫发作有关，癫痫发作可能会加剧随后的缺氧缺血性脑病。在 BA 啮齿动物模型中，暴露于缺氧环境被用来诱发癫痫发作，癫痫发作在损伤期间就已经开始。这与临床 BA 形成鲜明对比，临床 BA 中通常在恢复后出现癫痫发作。在这里，我们介绍了一种相当于术语的 BA 大鼠模型，其中暴露于窒息后会引发癫痫发作。方法 出生后第 11-12 天的雄性大鼠幼崽暴露于持续窒息（15 分钟；含有 5% O2 + 20% CO2 的空气）或间歇性窒息（30 分钟；三个 5 + 5 分钟循环的 9% 和 5% O2）在 20% CO2 下）。记录自由行为动物的皮质活动和电图癫痫发作。在聚氨酯麻醉下同时进行皮质内 pH、Po2 和局部场电位 (LFP) 的电极测量。结果两种方案均将血液pH值降低至<7.0，将脑部pH值从7.3降低至6.7，并导致碱过量下降20 mmol·L-1。间歇性但非稳定的窒息后会引发电图癫痫发作，并伴有整个拉辛量表的抽搐。在 20% CO2 存在的情况下，大脑 Po2 仅短暂地受到 9% 环境 O2 的影响，但在达到 5% O2 的过程中降至检测水平以下，并且 LFP 活性几乎消失。当 5% CO2 减缓大脑 pH 值恢复时，窒息后癫痫发作受到强烈抑制。意义 大脑 pH 值恢复速度对窒息后癫痫发作倾向有很大影响。间歇性窒息时反复发生的缺氧会促进神经元兴奋，只有在高碳酸血症的抑制作用解除后才会导致癫痫发作。 据我们所知，目前的 BA 啮齿动物模型是第一个模型，其中与临床 BA 一致，行为和电图癫痫发作是在模拟 BA 的侮辱之后而不是期间触发的。