Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Neurosci. 2011 Oct 19;31(42):14850-60. doi: 10.1523/JNEUROSCI.3922-11.2011.
Cyclooxygenase-2 (COX-2), a source of inflammatory mediators and a multifunctional neuronal modulator, is rapidly induced in select populations of cortical neurons after status epilepticus. The consequences of rapid activity-triggered induction of COX-2 in neurons have been the subject of much study and speculation. To address this issue directly, we created a mouse in which COX-2 is conditionally ablated in selected forebrain neurons. Results following pilocarpine-induced status epilepticus indicate that neuronal COX-2 promotes early neuroprotection and then delayed neurodegeneration of CA1 pyramidal neurons, promotes neurodegeneration of nearby somatostatin interneurons in the CA1 stratum oriens and dentate hilus (which themselves do not express COX-2), intensifies a broad inflammatory reaction involving numerous cytokines and other inflammatory mediators in the hippocampus, and is essential for development of a leaky blood-brain barrier after seizures. These findings point to a profound role of seizure-induced neuronal COX-2 expression in neuropathologies that accompany epileptogenesis.
环氧化酶-2（COX-2）是炎症介质的来源和多功能神经元调节剂，在癫痫发作后可迅速诱导选择性皮质神经元中表达。快速活动触发神经元中 COX-2 的诱导的后果一直是许多研究和推测的主题。为了直接解决这个问题，我们创建了一种条件性地在选定的前脑神经元中缺失 COX-2 的小鼠。在匹罗卡品诱导的癫痫持续状态后得到的结果表明，神经元 COX-2 促进了早期神经保护，然后导致 CA1 锥体神经元的迟发性神经退行性变，促进了 CA1 层状或门区和齿状回中附近生长抑素中间神经元的神经退行性变（这些神经元本身不表达 COX-2），增强了广泛的炎症反应，涉及海马中的许多细胞因子和其他炎症介质，并且对于癫痫发作后血脑屏障的渗漏是必需的。这些发现表明，癫痫发作诱导的神经元 COX-2 表达在癫痫发生伴随的神经病理学中起着深远的作用。
