Ravizza T, Vezzani A
Laboratory of Experimental Neurology, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milano, Italy.
Neuroscience. 2006;137(1):301-8. doi: 10.1016/j.neuroscience.2005.07.063. Epub 2005 Nov 11.
Interleukin-1beta is rapidly synthesized by glia after the induction of seizures. Recent evidence shows that endogenous IL-1beta has proconvulsant actions mediated by interleukin-1 receptor type I. This receptor also mediates interleukin-1beta effects on neuronal susceptibility to neurotoxic insults. In this study, we investigated the basal and seizure-induced expression of interleukin-1 receptor type I in rat forebrain to identify the cells targeted by interleukin-1beta during epileptic activity. Self-sustained limbic status epilepticus was induced in rats by electrical stimulation of the ventral hippocampus. Interleukin-1 receptor type I immunoreactivity was barely detectable in neurons in control brain tissue. During status epilepticus, interleukin-1 receptor type I was induced in the hippocampal neurons firstly, and several hours later in astrocytes localized in limbic and extralimbic areas. Neuronal interleukin-1 receptor type I expression in the hippocampus outlasted the duration of spontaneous electroencephalographic seizure and was not observed in degenerating neurons. Astrocytic expression occurred transiently, between six and 18 h after the induction of status epilepticus and was invariably found in regions of neuronal damage. These time-dependent, cell- and region-specific changes in interleukin-1 receptor type I expression during status epilepticus suggest that interleukin-1 receptor type I in neurons mediates interleukin-1beta-induced fast changes in hippocampal excitability while interleukin-1 receptor type I receptors in astrocytes may mediate interleukin-1beta effects on neuronal survival in hostile conditions.
癫痫发作诱导后，胶质细胞会迅速合成白细胞介素-1β。最近的证据表明，内源性白细胞介素-1β具有由I型白细胞介素-1受体介导的促惊厥作用。该受体还介导白细胞介素-1β对神经元对神经毒性损伤易感性的影响。在本研究中，我们调查了大鼠前脑I型白细胞介素-1受体的基础表达和癫痫发作诱导后的表达，以确定癫痫活动期间白细胞介素-1β作用的细胞靶点。通过电刺激腹侧海马体在大鼠中诱导出自我维持的边缘性癫痫持续状态。在对照脑组织的神经元中几乎检测不到I型白细胞介素-1受体免疫反应性。在癫痫持续状态期间，海马神经元中首先诱导出I型白细胞介素-1受体，数小时后在位于边缘和边缘外区域的星形胶质细胞中诱导出该受体。海马体中神经元I型白细胞介素-1受体的表达持续时间超过了自发性脑电图癫痫发作的持续时间，并且在退化的神经元中未观察到。星形胶质细胞的表达是短暂的，在癫痫持续状态诱导后6至18小时之间出现，并且总是在神经元损伤区域中发现。癫痫持续状态期间I型白细胞介素-1受体表达的这些时间依赖性、细胞和区域特异性变化表明，神经元中的I型白细胞介素-1受体介导白细胞介素-1β诱导的海马兴奋性快速变化，而星形胶质细胞中的I型白细胞介素-1受体可能介导白细胞介素-1β在不利条件下对神经元存活的影响。
