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左乙拉西坦经鼻内和口服给药对 KA 诱导的 SE 大鼠模型中 SV2A 的时空分布的影响。

Effect of intranasal and oral administration of levetiracetam on the temporal and spatial distributions of SV2A in the KA-induced rat model of SE.

机构信息

Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China.

Department of Neurology, Qingdao Women and Children's Hospital of Qingdao University, Qingdao University, Qingdao, China.

出版信息

J Cell Mol Med. 2023 Dec;27(24):4045-4055. doi: 10.1111/jcmm.17986. Epub 2023 Oct 16.

Abstract

To investigate the effectiveness of nasal delivery of levetiracetam (LEV) on the distributions of synaptic vesicle protein 2 isoform A (SV2A) in epileptic rats with injection of kainic acid (KA) into amygdala. A total of 138 rats were randomly divided into four groups, including the Sham surgery group, the epilepsy group (EP), and the LEV oral administration (LPO) and nasal delivery (LND) groups. The rat intra-amygdala KA model of epilepsy was constructed. Pathological changes of rat brain tissue after status epilepticus (SE) were detected using haematoxylin and eosin staining. Expression of SV2A in rat hippocampus after SE was evaluated using the western blotting analysis. Expression and distribution of SV2A in rat hippocampus after SE were detected based on immunofluorescence staining. The EP group showed evident cell loss and tissue necrosis in the CA3 area of hippocampus, whereas the tissue damage in both LPO and LND groups was significantly reduced. Western blotting analysis showed that the expressions of SV2A in the hippocampus of both EP and LND groups were significantly decreased 1 week after SE, increased to the similar levels of the Sham group in 2 weeks, and continuously increased 4 weeks after SE to the level significantly higher than that of the Sham group. Results of immunofluorescence revealed largely the same expression patterns of SV2A in the CA3 area of hippocampus as those in the entire hippocampus. Our study revealed the same antiepileptic and neuronal protective effects by the nasal and oral administrations of LEV, without changing the expression level of SV2A.

摘要

为了研究鼻腔给予左乙拉西坦(LEV)对侧脑室注射红藻氨酸(KA)致痫大鼠突触囊泡蛋白 2 同工型 A(SV2A)分布的影响。将 138 只大鼠随机分为假手术组、癫痫组(EP)、LEV 口服(LPO)组和鼻腔给药(LND)组,每组 39 只。建立大鼠杏仁核 KA 癫痫模型,HE 染色观察 SE 后大鼠脑组织的病理变化,Western blot 检测 SE 后大鼠海马 SV2A 的表达,免疫荧光检测 SV2A 在大鼠海马的表达和分布。EP 组大鼠海马 CA3 区可见明显的细胞丢失和组织坏死,LPO 和 LND 组大鼠脑组织损伤明显减轻。Western blot 分析显示,SE 后 1 周 EP 和 LND 组大鼠海马 SV2A 表达明显降低,2 周时升高至与假手术组相似水平,4 周时持续升高至明显高于假手术组水平。免疫荧光结果显示,SV2A 在海马 CA3 区的表达与全海马具有相似的表达模式。本研究表明,LEV 经鼻腔和口服给药具有相同的抗癫痫和神经元保护作用,不改变 SV2A 的表达水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3835/10746941/05b0bd64b8a2/JCMM-27-4045-g004.jpg

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