Seizure-Induced Acute Glial Activation in the in vitro Isolated Guinea Pig Brain.
Seizure-Induced Acute Glial Activation in the in vitro Isolated Guinea Pig Brain.
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DOI：
10.3389/fneur.2021.607603
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发表时间：
2021
影响因子：
3.4
通讯作者：
Librizzi L
中科院分区：
文献类型：
--
作者：
Vila Verde D;de Curtis M;Librizzi L
简介：已经提出癫痫发作诱导星形胶质细胞中的IL-1β生物合成并增加血脑屏障（BBB）通透性，即使不存在血液传播的炎性分子和白细胞。在本研究中，我们研究癫痫发作是否会诱导通常在激活的神经胶质细胞中观察到的形态学变化。此外，我们将测试血清白蛋白外渗到脑实质中是否通过诱导星形胶质细胞和小胶质细胞活化而加剧神经元过度兴奋。研究方法：在离体豚鼠脑制备物中，通过动脉灌注甲碘荷包牡丹碱（BMI; 50 μM）在边缘区诱导癫痫样癫痫样事件（SLE）。在海马CA 1区和内侧内嗅皮层记录场电位。通过分析动脉灌注的异硫氰酸荧光素（FITC）-白蛋白的外渗来评估BBB通透性的变化。应用BMI与或不与人血清白蛋白共灌注后，在海马腹侧CA 1区用三维重建和Sholl分析评价星形胶质细胞和小胶质细胞的形态学变化。结果如下：BMI诱导的SLE促进了星形胶质细胞和小胶质细胞的形态学变化，使其成为活化的表型，通过定量其过程的数量和长度来证实。SLE诱导的血脑屏障损伤导致人重组白蛋白外渗，使SLE病程和活化的神经胶质细胞表型恶化。讨论内容：我们的研究提供了第一个直接的证据表明，SLE活动本身能够促进星形胶质细胞和小胶质细胞的激活，正如观察到的表型变化，在大脑区域参与癫痫发作的产生;我们还假设，胶质细胞增生，显着加剧h-重组白蛋白外渗从血流到脑实质由于SLE诱导的血脑屏障破坏，是负责癫痫发作活动的加强。
Introduction: It has been proposed that seizures induce IL-1β biosynthesis in astrocytes and increase blood brain barrier (BBB) permeability, even without the presence of blood borne inflammatory molecules and leukocytes. In the present study we investigate if seizures induce morphological changes typically observed in activated glial cells. Moreover, we will test if serum albumin extravasation into the brain parenchyma exacerbates neuronal hyperexcitability by inducing astrocytic and microglial activation. Methods: Epileptiform seizure-like events (SLEs) were induced in limbic regions by arterial perfusion of bicuculline methiodide (BMI; 50 μM) in the in vitro isolated guinea pig brain preparation. Field potentials were recorded in both the hippocampal CA1 region and the medial entorhinal cortex. BBB permeability changes were assessed by analyzing extravasation of arterially perfused fluorescein isothiocyanate (FITC)–albumin. Morphological changes in astrocytes and microglia were evaluated with tridimensional reconstruction and Sholl analysis in the ventral CA1 area of the hippocampus following application of BMI with or without co-perfusion of human serum albumin. Results: BMI-induced SLE promoted morphological changes of both astrocytes and microglia cells into an activated phenotype, confirmed by the quantification of the number and length of their processes. Human-recombinant albumin extravasation, due to SLE-induced BBB impairment, worsened both SLE duration and the activated glia phenotype. Discussion: Our study provides the first direct evidence that SLE activity per se is able to promote the activation of astro- and microglial cells, as observed by their changes in phenotype, in brain regions involved in seizure generation; we also hypothesize that gliosis, significantly intensified by h-recombinant albumin extravasation from the bloodstream to the brain parenchyma due to SLE-induced BBB disruption, is responsible for seizure activity reinforcement.
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影响因子：
5.3
作者：
Djukic, Biljana;Casper, Kristen B.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
影响因子：
5.6
作者：
Benson, Melissa J.;Manzanero, Silvia;Borges, Karin
通讯作者：
Borges, Karin
影响因子：
2.5
作者：
Biella, G;De Curtis, M
通讯作者：
De Curtis, M
影响因子：
4.7
作者：
Hooper, C;Taylor, DL;Pocock, JM
通讯作者：
Pocock, JM
影响因子：
4.7
作者：
Hooper, Claudie;Pinteaux-Jones, Fleur;Pocock, Jennifer M.
通讯作者：
Pocock, Jennifer M.