Brain-on-a-chip microsystem for investigating traumatic brain injury: Axon diameter and mitochondrial membrane changes play a significant role in axonal response to strain injuries.
Brain-on-a-chip microsystem for investigating traumatic brain injury: Axon diameter and mitochondrial membrane changes play a significant role in axonal response to strain injuries.
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DOI：
10.1142/s2339547814500095
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Yarmush ML
中科院分区：
文献类型：
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作者：
Dollé JP;Morrison B 3rd;Schloss RS;Yarmush ML
弥漫性轴突损伤（DAI）是创伤性脑损伤的毁灭性后果，导致显着的轴突和神经元变性。目前，治疗选择有限。使用我们的片上大脑设备，我们评估了 DAI 的轴突反应。我们观察到轴突直径在应变损伤的反应中起着重要作用，这与弹性延迟相关，与轴突串珠和轴突变性呈负相关。当监测线粒体膜电位（MMP）的变化时，注意到施加的应变损伤阈值，低于该阈值则观察到延迟超极化，高于该阈值则发生立即去极化。当损伤前给予 NHE-1 抑制剂 EIPA 时，超极化和去极化的抑制以及轴突变性都发生。因此，轴突直径在应变损伤中起着重要作用，我们的脑芯片技术既可用于了解 DAI 的生化后果，又可用于筛选潜在的治疗药物。
Diffuse axonal injury (DAI) is a devastating consequence of traumatic brain injury, resulting in significant axon and neuronal degeneration. Currently, therapeutic options are limited. Using our brain-on-a-chip device, we evaluated axonal responses to DAI. We observed that axonal diameter plays a significant role in response to strain injury, which correlated to delayed elasticity and inversely correlated to axonal beading and axonal degeneration. When changes in mitochondrial membrane potential (MMP) were monitored an applied strain injury threshold was noted, below which delayed hyperpolarization was observed and above which immediate depolarization occurred. When the NHE-1 inhibitor EIPA was administered before injury, inhibition in both hyperpolarization and depolarization occurred along with axonal degeneration. Therefore, axonal diameter plays a significant role in strain injury and our brain-on-a-chip technology can be used both to understand the biochemical consequences of DAI and screen for potential therapeutic agents.