Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, USA.
J Cereb Blood Flow Metab. 2022 Oct;42(10):1777-1796. doi: 10.1177/0271678X221111600. Epub 2022 Jun 29.
Brain ischemia affects all ages, from neonates to the elderly population, and is a leading cause of mortality and morbidity. Multiple preclinical rodent models involving different ages have been developed to investigate the effect of ischemia during different times of key brain maturation events. Traditional models of developmental brain ischemia have focused on rodents at postnatal day 7-10, though emerging models in juvenile rodents (postnatal days 17-25) indicate that there may be fundamental differences in neuronal injury and functional outcomes following focal or global cerebral ischemia at different developmental ages, as well as in adults. Here, we consider the timing of injury in terms of excitation/inhibition balance, oxidative stress, inflammatory responses, blood brain barrier integrity, and white matter injury. Finally, we review translational strategies to improve function after ischemic brain injury, including new ideas regarding neurorestoration, or neural repair strategies that restore plasticity, at delayed time points after ischemia.
脑缺血影响所有年龄段，从新生儿到老年人群，是死亡率和发病率的主要原因。已经开发了多种涉及不同年龄的临床前啮齿动物模型，以研究在关键大脑成熟事件的不同时间发生缺血的影响。发育性脑缺血的传统模型主要集中在出生后 7-10 天的啮齿动物上，尽管新生啮齿动物（出生后 17-25 天）的新兴模型表明，在不同发育年龄、以及成年后，在局灶性或全脑缺血后，神经元损伤和功能结果可能存在根本差异。在这里，我们考虑损伤的时间，涉及兴奋/抑制平衡、氧化应激、炎症反应、血脑屏障完整性和白质损伤。最后，我们回顾了改善缺血性脑损伤后功能的转化策略，包括关于神经修复或神经修复策略的新想法，这些策略可以在缺血后延迟时间点恢复可塑性。
