Mapping of neuronal networks underlying generalized seizures induced by increasing doses of pentylenetetrazol in the immature and adult rat:: a c-Fos immunohistochemical study
Mapping of neuronal networks underlying generalized seizures induced by increasing doses of pentylenetetrazol in the immature and adult rat:: a c-Fos immunohistochemical study
复制标题
在未成熟和成年大鼠中增加戊四唑剂量诱导全身性癫痫发作的神经元网络图谱：c-Fos 免疫组织化学研究
DOI：
10.1046/j.1460-9568.1998.00223.x
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发表时间：
1998-06-01
影响因子：
3.4
通讯作者：
Nehlig, A
中科院分区：
文献类型：
--
作者：
André, V;Pineau, N;Nehlig, A
本课题组先前的研究表明，戊四氮（PTZ）诱导的癫痫持续状态（SE）导致未成年大鼠年龄依赖性的急性和长期代谢和循环变化。为了根据年龄确定PTZ癫痫发作涉及的神经基质，本研究的目的是绘制10日龄（P10），21日龄（P21）和成年大鼠癫痫发作严重程度增加期间的细胞激活区域。通过反复注射亚惊厥剂量的PTZ诱导癫痫发作。动物接受的总剂量范围为4 - 125 mg/kg。这些剂量诱导了各种癫痫发作特征，包括失神样、阵挛性癫痫发作和SE。在癫痫发作后2 h，以动物中c-Fos免疫反应细胞的密度测量细胞活化。在P10大鼠接受行为非活性剂量的PTZ，c-Fos免疫反应性只出现在杏仁核。40 mg/kg剂量引起失神样癫痫发作，导致内侧丘脑、部分皮质区和苍白球中c-Fos表达减弱。阵挛性发作加强标记在以前的领域，并诱导扩散的c-Fos免疫反应的其他皮质区，丘脑，下丘脑和一些脑干核。在那个年龄，只有SE导致广泛和更强的c-Fos表达，然而，在中脑完全缺乏，在脑干和前脑边缘系统（包括海马）中仍然不完整。在P21和成年大鼠中，非活性剂量的PTZ诱导丘脑和下丘脑的c-Fos免疫反应。在失神样癫痫发作时，c-Fos标记扩散到大脑皮层、杏仁核、隔和脑干的某些区域。与阵挛性癫痫发作，免疫反应性增强，在所有领域已经激活的失神样癫痫发作，并出现在纹状体，脑干和海马，除了在CA 1。SE后，c-Fos在各脑区均有强表达。与成年大鼠相比，在P21的大部分区域中c-Fos标记的强度更高。这些数据与P10大鼠中细胞和突触连接的不成熟性、大鼠在生命的第三周期间对各种癫痫发作的已知更大敏感性以及PTZ癫痫发作所涉及的神经基质的性质一致。
Previous studies from our group have shown that pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to age-dependent acute and long-term metabolic and circulatory changes in immature rats. In order to define the neural substrates involved in PTZ seizures according to age, the purpose of the present study was to map the areas of cellular activation during seizures of increasing severity in 10-day-old (P10), 21-day-old (P21) and adult rats. Seizures were induced by repetitive injections of subconvulsive doses of PTZ. The total dose received by the animals ranged from 4 to 125 mg/kg. These doses induced a variety of seizure profiles including absence-like, clonic seizures and SE. The cellular activation was measured as the density of c-Fos immunoreactive cells in animals at 2 h after the onset of the seizures. In P10 rats receiving a behaviourally non-active dose of PTZ, c-Fos immunoreactivity appeared only in the amygdala. The dose of 40 mg/kg that induced absence-like seizures led to a weak c-Fos expression in the medial thalamus, some cortical areas and globus pallidus. Clonic seizures reinforced labelling in the previous areas and induced a spread of c-Fos immunoreactivity to other cortical areas, thalamus, hypothalamus and some brainstem nuclei. At that age, only SE led to a widespread and stronger expression of c-Fos which was, however, totally lacking in the midbrain, and remained incomplete in the brainstem and forebrain limbic system, including the hippocampus. In P21 and adult rats, the inactive dose of PTZ induced c-Fos immunoreactivity in thalamus and hypothalamus. With absence-like seizures, c-Fos labelling spread to the cerebral cortex, amygdala, septum and some brainstem regions. With clonic seizures, immunoreactivity was reinforced in all areas already activated by absence-like seizures, and appeared in the striatum, accumbens, brainstem and hippocampus, except in CA1. After SE, c-Fos was strongly expressed in all brain areas. The intensity of c-Fos labelling was higher in most regions of P21 compared to adult rats. These data are in agreement with the immaturity of cellular and synaptic connectivity in P10 rats, the known greater sensitivity of rats to various kinds of seizures during the third week of life and the nature of the neural substrates involved in PTZ seizures.