This is a new experimental, Chinese paper about brain injury supporting iron chelation as a treatment. ATH has been doing corresponding studies ( most likely with its iron chelators as ATH434) but has not published anything. For possible clinical usage of ATH434 in brain trauma we may perhaps need only a phase 2-3 study because ph1 has been done and "soon" we have a ph2 done ( July 2024). Brain trauma is a huge indication of iron chelation as explained in this paper.

Brain Res

. 2023 May 4;148383.

doi: 10.1016/j.brainres.2023.148383. Online ahead of print.

Deferoxamine ameliorates neurological dysfunction by inhibiting ferroptosis and neuroinflammation after traumatic brain injury

Haoran Jia ¹, Xilei Liu ², Yiyao Cao ¹, Hanhong Niu ³, LanZhang ⁴, RuiJun Li ⁵, Fanjian Li ¹, Dongdong Sun ⁶, Mingming Shi ⁷, Liang Wa ⁸, Xiao Liu ⁷, Guili Yang ⁷, Fanglian Chen ⁷, Shu Zhang ⁹, Jianning Zhang ¹⁰

Affiliations expand

• PMID: 37149247

DOI: 10.1016/j.brainres.2023.148383

Abstract

Traumatic brain injury (TBI) is an important reason of neurological damage and has high morbidity and mortality rates. The secondary damage caused by TBI leads to a poor clinical prognosis. According to the literature, TBI leads to ferrous iron aggregation at the site of trauma and may be a key factor in secondary injury. Deferoxamine (DFO), which is an iron chelator, has been shown to inhibit neuron degeneration; however, the role of DFO in TBI is unclear. The purpose of this study was to explore whether DFO can ameliorate TBI by inhibiting ferroptosis and neuroinflammation. Here, our findings suggest that DFO can reduce the accumulation of iron, lipid peroxides, and reactive oxygen species (ROS) and modulate the expression of ferroptosis-related indicators. Moreover, DFO may reduce NLRP3 activation via the ROS/NF-κB pathway, modulate microglial polarization, reduce neutrophil and macrophage infiltration, and inhibit the release of inflammatory factors after TBI. Additionally, DFO may reduce the activation of neurotoxic responsive astrocytes. Finally, we demonstrated that DFO can protect motor memory function, reduce edema and improve peripheral blood perfusion at the site of trauma in mice with TBI, as shown by behavioral experiments such as the Morris water maze test, cortical blood perfusion assessment and animal MRI. In conclusion, DFO ameliorates TBI by reducing iron accumulation to alleviate ferroptosis and neuroinflammation, and these findings provide a new therapeutic perspective for TBI.