Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA.
Int J Mol Sci. 2020 Jan 16;21(2):588. doi: 10.3390/ijms21020588.
Mild traumatic brain injury (TBI) often results in pathophysiological damage that can manifest as both acute and chronic neurological deficits. In an attempt to repair and reconnect disrupted circuits to compensate for loss of afferent and efferent connections, maladaptive circuitry is created and contributes to neurological deficits, including post-concussive symptoms. The TBI-induced pathology physically and metabolically changes the structure and function of neurons associated with behaviorally relevant circuit function. Complex neurological processing is governed, in part, by circuitry mediated by primary and modulatory neurotransmitter systems, where signaling is disrupted acutely and chronically after injury, and therefore serves as a primary target for treatment. Monitoring of neurotransmitter signaling in experimental models with technology empowered with improved temporal and spatial resolution is capable of recording in vivo extracellular neurotransmitter signaling in behaviorally relevant circuits. Here, we review preclinical evidence in TBI literature that implicates the role of neurotransmitter changes mediating circuit function that contributes to neurological deficits in the post-acute and chronic phases and methods developed for in vivo neurochemical monitoring. Coupling TBI models demonstrating chronic behavioral deficits with in vivo technologies capable of real-time monitoring of neurotransmitters provides an innovative approach to directly quantify and characterize neurotransmitter signaling as a universal consequence of TBI and the direct influence of pharmacological approaches on both behavior and signaling.
轻度创伤性脑损伤 (TBI) 常导致病理生理学损伤，表现为急性和慢性神经功能缺损。为了修复和重新连接中断的回路以代偿传入和传出连接的丧失，适应性回路会被创建，从而导致神经功能缺损，包括脑震荡后症状。TBI 引起的病理改变会导致与行为相关回路功能相关的神经元的结构和功能发生物理和代谢变化。复杂的神经处理部分由主要和调节性神经递质系统介导的回路控制，其中信号在损伤后急性和慢性中断，因此是治疗的主要靶点。具有改进的时空分辨率的技术赋能的实验模型中的神经递质信号监测能够记录行为相关回路中的活体细胞外神经递质信号。在这里，我们回顾了 TBI 文献中的临床前证据，这些证据表明神经递质变化在调节回路功能中起作用，这导致了急性期和慢性期后的神经功能缺损，以及为活体神经化学监测开发的方法。将表现出慢性行为缺陷的 TBI 模型与能够实时监测神经递质的活体技术相结合，为直接定量和描述神经递质信号提供了一种创新方法，这是 TBI 的普遍后果，也是药理学方法对行为和信号的直接影响。
