Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy.
Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy.
复制标题
DOI：
10.3389/fcell.2022.867949
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
Thippeswamy T
中科院分区：
文献类型：
--
作者：
Gage M;Gard M;Thippeswamy T
在脊髓和大脑刺伤后观察到神经胶质疤痕，但在化学惊厥诱发的癫痫模型中未观察到和表征。癫痫是一种以自发性反复发作为特征的疾病，可以在啮齿类动物中进行建模。与现实世界中化学战场景中使用的其他有机磷神经毒剂 (OPNA) 一样，二异丙基氟磷酸盐 (DFP) 暴露可能导致癫痫持续状态 (SE)。我们之前已经证明，DFP 诱导的 SE 会促进癫痫发生，其特征是自发性复发性癫痫发作 (SRS)、神经胶质增生和神经变性的发生。在这项研究中，我们报告了暴露后 8 天在梨状皮层而非海马体中形成的经典神经胶质疤痕。我们用 4-5 mg/kg DFP（皮下注射）对雄性和雌性大鼠进行攻击，然后立即注射 2 mg/kg 硫酸阿托品（肌肉注射）和 25 mg/kg 解磷定（肌肉注射），一小时后注射咪达唑仑（肌肉注射）。 73% 的 DFP 治疗动物的梨状皮层/杏仁核区域存在神经胶质疤痕。对照中没有发现疤痕。疤痕的特征是大量反应性小胶质细胞聚集，周围环绕着肥大的反应性星形胶质细胞。与疤痕周边相比，疤痕核心充满了IBA1和CD68阳性细胞显着增加，NeuN阳性细胞显着减少。与对照组的类似区域相比，疤痕周围的反应性 GFAP、补体 3 (C3) 和诱导型一氧化氮合酶 (iNOS) 阳性细胞的密度明显更高。我们发现，与对照大脑中的类似区域相比，疤痕周围的硫酸软骨素蛋白聚糖（CS-56）显着增加。然而，与对照组相比，DFP 暴露动物的疤痕内或周围的 TGF-β1 或 TGF-β2 阳性细胞没有变化。与刺伤引起的疤痕相反，我们在疤痕核心或周围没有发现成纤维细胞 (Thy1.1)。 iNOS、CD68、NeuN、GFAP、C3 和 CS-56 阳性细胞的密度存在性别差异。这是首次报道啮齿类动物因全身化学惊厥引起的 SE 出现皮质胶质疤痕。进一步的研究可能有助于阐明疤痕形成的机制和缓解策略。
Glial scars have been observed following stab lesions in the spinal cord and brain but not observed and characterized in chemoconvulsant-induced epilepsy models. Epilepsy is a disorder characterized by spontaneous recurrent seizures and can be modeled in rodents. Diisopropylfluorophosphate (DFP) exposure, like other real-world organophosphate nerve agents (OPNAs) used in chemical warfare scenarios, can lead to the development of status epilepticus (SE). We have previously demonstrated that DFP-induced SE promotes epileptogenesis which is characterized by the development of spontaneous recurrent seizures (SRS), gliosis, and neurodegeneration. In this study, we report classical glial scars developed in the piriform cortex, but not in the hippocampus, by 8 days post-exposure. We challenged both male and female rats with 4–5 mg/kg DFP (s.c.) followed immediately by 2 mg/kg atropine sulfate (i.m.) and 25 mg/kg pralidoxime (i.m.) and one hour later by midazolam (i.m). Glial scars were present in the piriform cortex/amygdala region in 73% of the DFP treated animals. No scars were found in controls. Scars were characterized by a massive clustering of reactive microglia surrounded by hypertrophic reactive astrocytes. The core of the scars was filled with a significant increase of IBA1 and CD68 positive cells and a significant reduction in NeuN positive cells compared to the periphery of the scars. There was a significantly higher density of reactive GFAP, complement 3 (C3), and inducible nitric oxide synthase (iNOS) positive cells at the periphery of the scar compared to similar areas in controls. We found a significant increase in chondroitin sulfate proteoglycans (CS-56) in the periphery of the scars compared to a similar region in control brains. However, there was no change in TGF-β1 or TGF-β2 positive cells in or around the scars in DFP-exposed animals compared to controls. In contrast to stab-induced scars, we did not find fibroblasts (Thy1.1) in the scar core or periphery. There were sex differences with respect to the density of iNOS, CD68, NeuN, GFAP, C3 and CS-56 positive cells. This is the first report of cortical glial scars in rodents with systemic chemoconvulsant-induced SE. Further investigation could help to elucidate the mechanisms of scar development and mitigation strategies.
登录
查看更多内容
影响因子：
34.7
作者：
Clarke, Laura E.;Barres, Ben A.
通讯作者：
Barres, Ben A.
DOI：
10.1016/0167-5699(91)90009-i
发表时间：
1991-09-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
FRANK, MM;FRIES, LF
通讯作者：
FRIES, LF
影响因子：
3.4
作者：
Aroniadou-Anderjaska, Vassiliki;Figueiredo, Taiza H.;Braga, Maria F. M.
通讯作者：
Braga, Maria F. M.
影响因子：
2.2
作者：
Buss, A.;Pech, K.;Brook, G. A.
通讯作者：
Brook, G. A.
影响因子：
5.6
作者：
Beghi, Ettore;Hesdorffer, Dale
通讯作者：
Hesdorffer, Dale