Chandran Raghavendar, Mehta Suresh L, Vemuganti Raghu
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA.
William S. Middleton Veterans Administration Hospital, Madison, WI, USA.
Neuromolecular Med. 2021 Sep;23(3):344-347. doi: 10.1007/s12017-021-08645-3. Epub 2021 Jan 23.
Following traumatic brain injury (TBI), increased production of reactive oxygen species (ROS) and the ensuing oxidative stress promotes the secondary brain damage that encompasses both grey matter and white matter. As this contributes to the long-term neurological deficits, decreasing oxidative stress during the acute period of TBI is beneficial. While NADPH oxidase (NOX2) is the major producer of ROS, transcription factor Nrf2 that induces antioxidant enzymes promotes efficient ROS disposal. We recently showed that treatment with an antioxidant drug combo of apocynin (NOX2 inhibitor) and TBHQ (Nrf2 activator) protects the grey matter in adult mice subjected to TBI. We currently show that this antioxidant combo therapy given at 2 h and 24 h after TBI also protects white matter in mouse brain. Thus, the better functional outcomes after TBI in the combo therapy treated mice might be due to a combination of sparing both grey matter and white matter. Hence, the antioxidant combo we tested is a potent therapeutic option for translation in future.
创伤性脑损伤（TBI）后，活性氧（ROS）生成增加及随之而来的氧化应激会促进包括灰质和白质在内的继发性脑损伤。由于这会导致长期神经功能缺损，在TBI急性期降低氧化应激是有益的。虽然NADPH氧化酶（NOX2）是ROS的主要产生者，但诱导抗氧化酶的转录因子Nrf2可促进ROS的有效清除。我们最近发现，用载脂蛋白（NOX2抑制剂）和叔丁基对苯二酚（TBHQ，Nrf2激活剂）组成的抗氧化药物组合进行治疗，可保护遭受TBI的成年小鼠的灰质。我们目前发现，在TBI后2小时和24小时给予这种抗氧化组合疗法，也可保护小鼠脑白质。因此，接受组合疗法治疗的小鼠在TBI后功能恢复更好，可能是由于灰质和白质均得到了保护。因此，我们测试的这种抗氧化组合是未来具有转化潜力的有效治疗选择。
