Traumatic brain injury (TBI) constitutes a heterogeneous cerebral insult induced by traumatic biomechanical forces. Mitochondria play a critical role in brain bioenergetics, and TBI induces several consequences related with oxidative stress and excitotoxicity clearly demonstrated in different experimental model involving TBI. Mitochondrial bioenergetics alterations can present several targets for therapeutics which could help reduce secondary brain lesions such as neuropsychiatric problems, including memory loss and motor impairment. Guanosine (GUO), an endogenous neuroprotective nucleoside, affords the long-term benefits of controlling brain neurodegeneration, mainly due to its capacity to activate the antioxidant defense system and maintenance of the redox system. However, little is known about the exact protective mechanism exerted by GUO on mitochondrial bioenergetics disruption induced by TBI. Thus, the aim of this study was to investigate the effects of GUO in brain cortical and hippocampal mitochondrial bioenergetics in the mild TBI model. Additionally, we aimed to assess whether mitochondrial damage induced by TBI may be related to behavioral alterations in rats. Our findings showed that 24 h post-TBI, GUO treatment promotes an adaptive response of mitochondrial respiratory chain increasing oxygen flux which it was able to protect against the uncoupling of oxidative phosphorylation (OXPHOS) induced by TBI, restored the respiratory electron transfer system (ETS) established with an uncoupler. Guanosine treatment also increased respiratory control ratio (RCR), an indicator of the state of mitochondrial coupling, which is related to the mitochondrial functionality. In addition, mitochondrial bioenergetics failure was closely related with locomotor, exploratory and memory impairments. The present study suggests GUO treatment post mild TBI could increase GDP endogenous levels and consequently increasing ATP levels promotes an increase of RCR increasing OXPHOS and in substantial improve mitochondrial respiration in different brain regions, which, in turn, could promote an improvement in behavioral parameters associated to the mild TBI. These findings may contribute to the development of future therapies with a target on failure energetic metabolism induced by TBI.

创伤性脑损伤 (TBI) 是由外伤性生物力学力引起的异质脑损伤。线粒体在脑生物能量学中起着关键作用，TBI 会诱发与氧化应激和兴奋性毒性相关的几种后果，这在涉及 TBI 的不同实验模型中得到了明确证明。线粒体生物能量学的改变可以为治疗提供几个目标，这有助于减少继发性脑损伤，如神经精神问题，包括记忆力减退和运动障碍。鸟苷 (GUO) 是一种内源性神经保护核苷，可提供控制脑神经变性的长期益处，主要是由于其能够激活抗氧化防御系统和维持氧化还原系统。然而，关于 GUO 对 TBI 诱导的线粒体生物能学破坏的确切保护机制知之甚少。因此，本研究的目的是在轻度 TBI 模型中研究 GUO 对脑皮质和海马线粒体生物能量学的影响。此外，我们旨在评估 TBI 诱导的线粒体损伤是否可能与大鼠的行为改变有关。我们的研究结果表明，TBI 后 24 小时，GUO 治疗促进了线粒体呼吸链增加氧通量的适应性反应，它能够防止 TBI 诱导的氧化磷酸化 (OXPHOS) 解偶联，恢复呼吸电子转移系统 (ETS) ) 用解耦器建立。鸟苷治疗还增加了呼吸控制率（RCR），这是线粒体耦合状态的指标，这与线粒体功能有关。此外，线粒体生物能学失败与运动、探索和记忆障碍密切相关。目前的研究表明，轻度 TBI 后 GUO 治疗可以增加 GDP 内源性水平，因此增加 ATP 水平促进 RCR 增加，增加 OXPHOS 并显着改善不同大脑区域的线粒体呼吸，这反过来又可以促进相关行为参数的改善。到轻度 TBI。这些发现可能有助于未来疗法的发展，其目标是由 TBI 引起的能量代谢衰竭。目前的研究表明，轻度 TBI 后 GUO 治疗可以增加 GDP 内源性水平，因此增加 ATP 水平促进 RCR 增加，增加 OXPHOS 并显着改善不同大脑区域的线粒体呼吸，这反过来又可以促进相关行为参数的改善。到轻度 TBI。这些发现可能有助于未来疗法的发展，其目标是由 TBI 引起的能量代谢衰竭。目前的研究表明，轻度 TBI 后 GUO 治疗可以增加 GDP 内源性水平，因此增加 ATP 水平促进 RCR 增加，增加 OXPHOS 并显着改善不同大脑区域的线粒体呼吸，这反过来又可以促进相关行为参数的改善。到轻度 TBI。这些发现可能有助于未来疗法的发展，其目标是由 TBI 引起的能量代谢衰竭。