Department of Neurosurgery, 1st Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Department of Medicine and Management, Mudanjiang Chinese Traditional Medicine Hospital, Mudanjiang 157000, China.
Biosci Rep. 2017 Nov 6;37(6). doi: 10.1042/BSR20170942. Print 2017 Dec 22.
Oxidative stress has been strongly implicated in the pathogenesis of traumatic brain injury (TBI). Mitochondrial ferritin (Ftmt) is reported to be closely related to oxidative stress. However, whether Ftmt is involved in TBI-induced oxidative stress and neurological deficits remains unknown. In the present study, the controlled cortical impact model was established in wild-type and Ftmt knockout mice as a TBI model. The Ftmt expression, oxidative stress, neurological deficits, and brain injury were measured. We found that Ftmt expression was gradually decreased from 3 to 14 days post-TBI, while oxidative stress was gradually increased, as evidenced by reduced GSH and superoxide dismutase levels and elevated malondialdehyde and nitric oxide levels. Interestingly, the extent of reduced Ftmt expression in the brain was linearly correlated with oxidative stress. Knockout of Ftmt significantly exacerbated TBI-induced oxidative stress, intracerebral hemorrhage, brain infarction, edema, neurological severity score, memory impairment, and neurological deficits. However, all these effects in Ftmt knockout mice were markedly mitigated by pharmacological inhibition of oxidative stress using an antioxidant, N-acetylcysteine. Taken together, these results reveal an important correlation between Ftmt and oxidative stress after TBI. Ftmt deficiency aggravates TBI-induced brain injuries and neurological deficits, which at least partially through increasing oxidative stress levels. Our data suggest that Ftmt may be a promising molecular target for the treatment of TBI.
氧化应激在创伤性脑损伤（TBI）的发病机制中起着重要作用。线粒体铁蛋白（Ftmt）与氧化应激密切相关。然而，Ftmt 是否参与 TBI 诱导的氧化应激和神经功能缺损尚不清楚。在本研究中，采用野生型和 Ftmt 敲除小鼠建立皮质撞击模型作为 TBI 模型。测量了 Ftmt 表达、氧化应激、神经功能缺损和脑损伤。我们发现，Ftmt 表达从 TBI 后 3 天到 14 天逐渐下降，而氧化应激逐渐增加，表现为 GSH 和超氧化物歧化酶水平降低，丙二醛和一氧化氮水平升高。有趣的是，脑内 Ftmt 表达减少的程度与氧化应激呈线性相关。Ftmt 敲除显著加重了 TBI 诱导的氧化应激、脑出血、脑梗死、水肿、神经严重程度评分、记忆障碍和神经功能缺损。然而，用抗氧化剂 N-乙酰半胱氨酸抑制氧化应激对 Ftmt 敲除小鼠的所有这些作用均有明显缓解。综上所述，这些结果揭示了 TBI 后 Ftmt 与氧化应激之间的重要相关性。Ftmt 缺乏加重了 TBI 诱导的脑损伤和神经功能缺损，这至少部分是通过增加氧化应激水平实现的。我们的数据表明，Ftmt 可能是治疗 TBI 的有前途的分子靶点。
