Modeling Controlled Cortical Impact Injury in 3D Brain-Like Tissue Cultures.,Advanced Healthcare Materials

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Modeling Controlled Cortical Impact Injury in 3D Brain-Like Tissue Cultures.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-05-13 , DOI: 10.1002/adhm.202000122
Volha Liaudanskaya ₁ , Joon Yong Chung ₂ , Craig Mizzoni ₁ , Nicolas Rouleau ₁ , Alexander N Berk ₁ , Limin Wu ₂ , Julia A Turner ₁ , Irene Georgakoudi ₁ , Michael J Whalen ₂ , Thomas J F Nieland ₁ , David L Kaplan ₁

Affiliation

Traumatic brain injury (TBI) survivors suffer long term from mental illness, neurodegeneration, and neuroinflammation. Studies of 3D tissue models have provided new insights into the pathobiology of many brain diseases. Here, a 3D in vitro contusion model is developed consisting of mouse cortical neurons grown on a silk scaffold embedded in collagen and used outcomes from an in vivo model for benchmarking. Molecular, cellular, and network events are characterized in response to controlled cortical impact (CCI). In this model, CCI induces degradation of neural network structure and function and release of glutamate, which are associated with the expression of programmed necrosis marker phosphorylated Mixed Lineage Kinase Domain Like Pseudokinase (pMLKL). Neurodegeneration is observed first in the directly impacted area and it subsequently spreads over time in 3D space. CCI reduces phosphorylated protein kinase B (pAKT) and Glycogen synthase kinase 3 beta (GSK3β ) in neurons in vitro and in vivo, but discordant responses are observed in phosphprylated ribosomal S6 kinase (pS6) and phosphorylated Tau (pTau) expression. In summary, the 3D brain‐like culture system mimicked many aspects of in vivo responses to CCI, providing evidence that the model can be used to study the molecular, cellular, and functional sequelae of TBI, opening up new possibilities for discovery of therapeutics.

中文翻译：

在 3D 类脑组织培养中模拟受控皮质撞击损伤。

创伤性脑损伤 (TBI) 幸存者长期患有精神疾病、神经退行性疾病和神经炎症。 3D 组织模型的研究为许多脑部疾病的病理学提供了新的见解。在此，开发了一种 3D 体外挫伤模型，该模型由生长在嵌入胶原蛋白的丝支架上的小鼠皮质神经元组成，并使用体内模型的结果进行基准测试。分子、细胞和网络事件的特征是对受控皮质影响 (CCI) 的响应。在该模型中，CCI 诱导神经网络结构和功能的降解以及谷氨酸的释放，这与程序性坏死标记物磷酸化混合谱系激酶结构域样假激酶 (pMLKL) 的表达相关。首先在直接受影响的区域观察到神经退行性变，随后随着时间的推移在 3D 空间中扩散。 CCI 在体外和体内降低神经元中的磷酸化蛋白激酶 B (pAKT) 和糖原合酶激酶 3 beta (GSK3 β )，但在磷酸化核糖体 S6 激酶 (pS6) 和磷酸化 Tau (pTau) 表达中观察到不一致的反应。总之，3D类脑培养系统模仿了CCI体内反应的许多方面，提供了证据表明该模型可用于研究TBI的分子、细胞和功能后遗症，为发现治疗方法开辟了新的可能性。

更新日期：2020-06-24

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