Long-term intracerebroventricular infusion of angiotensin II after kainate-induced status epilepticus: Effects on epileptogenesis, brain damage, and diurnal behavioral changes
Long-term intracerebroventricular infusion of angiotensin II after kainate-induced status epilepticus: Effects on epileptogenesis, brain damage, and diurnal behavioral changes
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DOI：
10.1016/j.yebeh.2015.06.036
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发表时间：
2015-10-01
影响因子：
2.6
通讯作者：
Tchekalarova, Jana D.
中科院分区：
文献类型：
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作者：
Ivanova, Natasha M.;Atanasova, Dimitrina;Tchekalarova, Jana D.
我们先前的研究表明，血管紧张素II在急性癫痫模型中具有抗惊厥作用。然而，关于它在癫痫实验模型中的作用的数据尚不清楚。在本研究中，我们测试了红藻氨酸(KA)诱导的癫痫持续状态(SE)后应用血管紧张素转换酶II(Ang II)是否会影响癫痫的发生、伴随的行为变化和脑损伤。SE后，采用微量渗透压泵脑室内注射血管紧张素转换酶Ⅱ(AngⅡ，1.52ug/亩，L，每日1次，共28d)。对自发性运动性惊厥(SMS)进行长达三个月的录像。在用药后最后一周评估运动能力、焦虑和抑郁样行为，而在SE后3个月评估空间记忆。血管紧张素II缩短了首次短信的潜伏期，增加了SE后2个月的短信频率。持续的多肽输注加剧了KA诱导的多动，并导致抑郁样行为。Ang II可减轻KA处理大鼠的焦虑程度。Ang II不影响KA所致的海马区空间记忆障碍，但Ang II可部分阻止海马神经元的损伤，尤其是CA1区。讨论了AT(1)和AT(2)受体激活在八肽作用中的作用。(C)2015 Elsevier Inc.保留所有权利。
Our previous studies revealed that Angiotensin (Ang) II has anticonvulsant effects in acute seizure models. However, data on its role in experimental models of epilepsy are missing. In the present study, we tested whether posttreatment with Ang II after kainate (KA)-induced status epilepticus (SE) can affect epileptogenesis, concomitant behavioral changes, and brain damage. The Wistar rats were intracerebroventricularly infused via osmotic mini-pumps with Ang II (1.52 mu g/mu l/day for 28 days) after SE. Spontaneous motor seizures (SMS) were video-recorded for up to three months. Locomotor activity, anxiety, and depression-like behavior were evaluated during the last week of drug infusion, while spatial memory was assessed during the 3rd month after SE. Angiotensin II decreased the latency for onset of the first SMS and increased the frequency of SMS two months after SE. The continuous peptide infusion exacerbated the KA-induced hyperactivity and caused depression-like behavior. The reduced anxiety of KA-treated rats was alleviated by Ang II exposure. The KA-induced deficit in the hippocampal-dependent spatial memory was not influenced by Ang II. However, Ang II partially prevented the neuronal damage in the hippocampus, specifically in the CA1 area. The role of AT(1) and AT(2) receptor activation in the effects of the octapeptide is discussed. (C) 2015 Elsevier Inc. All rights reserved.