Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Neurosurgery, The First Medical Center of People's Liberation Army General Hospital, Beijing, China.
Department of Neurosurgery, The First Medical Center of People's Liberation Army General Hospital, Beijing, China.
Exp Neurol. 2024 Dec;382:114977. doi: 10.1016/j.expneurol.2024.114977. Epub 2024 Sep 30.
Traumatic brain injury (TBI) is a major cause of death and disability worldwide, with its severity potentially exacerbated by seawater immersion. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has been implicated in TBI pathogenesis. However, the specific occurrence and underlying mechanisms of ferroptosis in the context of TBI compounded by seawater immersion remain unclear. Subsequently, we investigated the effects of seawater immersion on ferroptosis after the application of deferoxamine (DFO), an iron chelator and ferroptosis inhibitor, to explore its potential therapeutic value. We conducted RNA sequencing, protein expression analysis, oxidative stress assessment, histopathological examination, and behavioral testing to comprehensively evaluate the impact of DFO on ferroptosis and neurological outcomes. Our results demonstrated that seawater immersion significantly exacerbated ferroptosis in TBI. DFO treatment, however, attenuated ferroptosis, alleviated oxidative stress, reduced brain tissue damage, improved neuronal survival, and promoted motor function recovery. Despite these benefits, DFO exhibited limited effects on anxiety, novel object recognition, and spatial learning and memory. These findings suggest that ferroptosis represents a novel pathological mechanism in TBI under seawater immersion, and that DFO is a promising neuroprotective agent capable of modulating ferroptosis and enhancing neurological function. This study offers new insights into the complex injury conditions associated with TBI and seawater immersion, highlighting the potential of targeting ferroptosis for therapeutic intervention.
创伤性脑损伤 (TBI) 是全球范围内导致死亡和残疾的主要原因，其严重程度可能因海水浸泡而加剧。铁死亡是一种由铁依赖性脂质过氧化驱动的细胞死亡形式，已被认为与 TBI 的发病机制有关。然而，在海水浸泡的情况下，TBI 中铁死亡的具体发生和潜在机制尚不清楚。随后，我们研究了在应用铁螯合剂和铁死亡抑制剂去铁胺 (DFO) 后，海水浸泡对铁死亡的影响，以探讨其潜在的治疗价值。我们进行了 RNA 测序、蛋白质表达分析、氧化应激评估、组织病理学检查和行为测试，以全面评估 DFO 对铁死亡和神经功能的影响。我们的结果表明，海水浸泡显著加剧了 TBI 中的铁死亡。然而，DFO 治疗减轻了铁死亡、氧化应激、脑损伤、神经元存活和运动功能恢复。尽管有这些好处，DFO 对焦虑、新物体识别、空间学习和记忆的影响有限。这些发现表明，铁死亡是海水浸泡下 TBI 的一种新的病理机制，DFO 是一种有前途的神经保护剂，能够调节铁死亡并增强神经功能。本研究为与 TBI 和海水浸泡相关的复杂损伤情况提供了新的见解，强调了针对铁死亡进行治疗干预的潜力。
