Traumatic brain injury (TBI) is an established risk factor for developing neurodegenerative disease. However, how TBI leads from acute injury to chronic neurodegeneration is limited to postmortem models. There is a lack of connections between in vitro and in vivo TBI models that can relate injury forces to both macroscale tissue damage and brain function at the cellular level. Needle-induced cavitation (NIC) is a technique that can produce small cavitation bubbles in soft tissues, which allows us to relate small strains and strain rates in living tissue to ensuing acute cell death, tissue damage, and tissue remodeling. Here, we applied NIC to mouse brain slices to create a new model of TBI with high spatial and temporal resolution. We specifically targeted the hippocampus, which is a brain region critical for learning and memory and an area in which injury causes cognitive pathologies in humans and rodent models. By combining NIC with patch-clamp electrophysiology, we demonstrate that NIC in the cornu ammonis 3 region of the hippocampus dynamically alters synaptic release onto cornu ammonis 1 pyramidal neurons in a cannabinoid 1 receptor-dependent manner. Further, we show that NIC induces an increase in extracellular matrix protein GFAP associated with neural repair that is mitigated by cannabinoid 1 receptor antagonism. Together, these data lay the groundwork for advanced approaches in understanding how TBI impacts neural function at the cellular level and the development of treatments that promote neural repair in response to brain injury.

中文翻译：

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海马体轻度创伤性脑损伤的短期神经和神经胶质反应


创伤性脑损伤 （TBI） 是发展为神经退行性疾病的既定风险因素。然而，TBI 如何从急性损伤导致慢性神经退行性变仅限于死后模型。体外和体内 TBI 模型之间缺乏联系，可以将损伤力与细胞水平的宏观组织损伤和脑功能联系起来。针诱导空化 （NIC） 是一种可以在软组织中产生小空化气泡的技术，它使我们能够将活组织中的小应变和应变率与随后的急性细胞死亡、组织损伤和组织重塑联系起来。在这里，我们将 NIC 应用于小鼠脑切片，以创建具有高空间和时间分辨率的新 TBI 模型。我们专门针对海马体，海马体是学习和记忆至关重要的大脑区域，也是受伤导致人类和啮齿动物模型认知病理的区域。通过将 NIC 与膜片钳电生理学相结合，我们证明海马体 cornu ammonis 3 区域的 NIC 以大麻素 1 受体依赖性方式动态改变 cornu ammonis 1 锥体神经元上的突触释放。此外，我们表明 NIC 诱导与神经修复相关的细胞外基质蛋白 GFAP 的增加，而大麻素 1 受体拮抗作用减轻了这种增加。总之，这些数据为了解 TBI 如何在细胞水平上影响神经功能以及开发促进神经修复以应对脑损伤的治疗方法奠定了基础。