Excessive reactive oxygen species (ROS) production can induce tissue injury involved in a variety of neurodegenerative disorders such as neurodegeneration observed in pilocarpine-induced temporal lobe epilepsy. Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist has beneficial effects in pilocarpine-induced temporal lobe epilepsy, when administered within minutes of seizure to avoid the harmful neurological lesions induced by pilocarpine. However, the enzymes involved in ROS productions and the effect of ketamine on this process remain less documented. Here we show that during pilocarpine-induced epilepsy in mice, the expression of the phagocyte NADPH oxidase NOX2 subunits (NOX2/gp91^phox, p22^phox, and p47^phox) and the expression of myeloperoxidase (MPO) were dramatically increased in mice brain treated with pilocarpine. Interestingly, treatment of mice with ketamine before or after pilocarpine administration decreased this process, mainly when injected before pilocarpine. Finally, our results showed that pilocarpine induced p47^phox phosphorylation and H₂O₂ production in mice brain and ketamine was able to inhibit these processes. Our results show that pilocarpine induced NOX2 activation to produce ROS in mice brain and that administration of ketamine before or after the induction of temporal lobe epilepsy by pilocarpine inhibited this activation in mice brain. These results suggest a key role of the phagocyte NADPH oxidase NOX2 and MPO in epilepsy and identify a novel effect of ketamine.

中文翻译：

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在毛果芸香碱诱导的颞叶癫痫和氯胺酮抑制过程中，小鼠脑中吞噬细胞NADPH氧化酶/ NOX2和髓过氧化物酶的激活。

过量的活性氧（ROS）产生会导致组织损伤，涉及多种神经退行性疾病，例如在毛果芸香碱诱发的颞叶癫痫中观察到神经变性。氯胺酮是一种非竞争性N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂，在癫痫发作的几分钟内给药可避免毛细果芸香碱诱发的颞叶癫痫发作，从而避免了毛细果芸香碱引起的有害神经病变。但是，参与ROS产生的酶和氯胺酮对此过程的影响仍然文献较少。在这里，我们显示了在毛果芸香碱诱发的小鼠癫痫中，吞噬细胞NADPH氧化酶NOX2亚基（NOX2 / gp91 ^phox，p22 ^phox和p47 ^{phox）的表达}），并且在用毛果芸香碱处理过的小鼠大脑中，髓过氧化物酶（MPO）的表达急剧增加。有趣的是，在给予毛果芸香碱之前或之后用氯胺酮治疗小鼠减少了这一过程，主要是在毛果芸香碱之前注射。最后，我们的结果表明毛果芸香碱诱导p47 ^phox磷酸化和H ₂ O ₂小鼠大脑和氯胺酮的产生能够抑制这些过程。我们的结果表明，毛果芸香碱会诱导NOX2活化，从而在小鼠脑中产生ROS，而在通过毛果芸香碱诱发颞叶癫痫发作之前或之后给予氯胺酮会抑制小鼠脑中的这种活化。这些结果表明吞噬细胞NADPH氧化酶NOX2和MPO在癫痫中起关键作用，并确定了氯胺酮的新作用。