New Insights into Oxidative Damage and Iron Associated Impairment in Traumatic Brain Injury

2020 ◽  
Vol 25 (45) ◽  
pp. 4737-4746
Author(s):  
Nicolas Toro-Urrego ◽  
Liliana F. Turner ◽  
Marco F. Avila-Rodriguez

: Traumatic Brain Injury is considered one of the most prevalent causes of death around the world; more than seventy millions of individuals sustain the condition per year. The consequences of traumatic brain injury on brain tissue are complex and multifactorial, hence, the current palliative treatments are limited to improve patients’ quality of life. The subsequent hemorrhage caused by trauma and the ongoing oxidative process generated by biochemical disturbances in the in the brain tissue may increase iron levels and reactive oxygen species. The relationship between oxidative damage and the traumatic brain injury is well known, for that reason, diminishing factors that potentiate the production of reactive oxygen species have a promissory therapeutic use. Iron chelators are molecules capable of scavenging the oxidative damage from the brain tissue and are currently in use for ironoverload- derived diseases. : Here, we show an updated overview of the underlying mechanisms of the oxidative damage after traumatic brain injury. Later, we introduced the potential use of iron chelators as neuroprotective compounds for traumatic brain injury, highlighting the action mechanisms of iron chelators and their current clinical applications.

2001 ◽  
Vol 21 (11) ◽  
pp. 1259-1267 ◽  
Author(s):  
Niklas Marklund ◽  
Tommy Lewander ◽  
Fredrik Clausen ◽  
Lars Hillered

In previous studies, the authors showed that the nitrone radical scavenger α-phenyl-N- tert-butyl nitrone (PBN) and its sulfo-derivative, 2-sulfo-phenyl-N- tert-butyl nitrone (S-PBN), attenuated cognitive disturbance and reduced tissue damage after traumatic brain injury (TBI) in rats. In the current study, the production of reactive oxygen species (ROS) after TBI was monitored with microdialysis and the 4-hydroxybenzoic acid (4-HBA) trapping method. A single dose of PBN (30 mg/kg) or an equimolar dose of S-PBN (47 mg/kg) was administered intravenously 30 minutes before a controlled cortical contusion injury in rats. Plasma and brain tissue drug concentrations were analyzed at the end of the microdialysis experiment (3 hours after injury) and, in a separate experiment with S-PBN, at 30 and 60 minutes after injury. Traumatic brain injury caused a significant increase in ROS formation that lasted for 60 minutes after the injury as evidenced by increased 3,4-dihydroxybenzoic acid (3,4-DHBA) concentrations in the dialysate. PBN and S-PBN equally and significantly attenuated the posttraumatic increase in 3,4-DHBA formation. High PBN concentrations were found bilaterally in brain tissue up to 3 hours after injury. In contrast, S-PBN was rapidly cleared from the circulation and was not detectable in brain at 30 minutes after injury or at any later time point. The results suggest that scavenging of ROS after TBI may contribute to the neuroprotective properties observed with nitrone spin-trapping agents. S-PBN, which remained undetectable even in traumatized brain tissue, reduced ROS production to the same extent as PBN that readily crossed the blood–brain barrier. This finding supports an important role for ROS production at the blood–endothelial interface in TBI.


PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61819 ◽  
Author(s):  
Morgan A. Clond ◽  
Bong-Seop Lee ◽  
Jeffrey J. Yu ◽  
Matthew B. Singer ◽  
Takayuki Amano ◽  
...  

2012 ◽  
Vol 173 (2) ◽  
pp. e73-e81 ◽  
Author(s):  
Brett E. Larson ◽  
David W. Stockwell ◽  
Stefan Boas ◽  
Trevor Andrews ◽  
George C. Wellman ◽  
...  

2020 ◽  
Vol 21 (5) ◽  
pp. 477-498
Author(s):  
Yongfeng Chen ◽  
Xingjing Luo ◽  
Zhenyou Zou ◽  
Yong Liang

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.


2021 ◽  
Vol 46 (1) ◽  
pp. 77-87
Author(s):  
Arnaud Tauffenberger ◽  
Pierre J. Magistretti

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.


2021 ◽  
Vol 11 (7) ◽  
pp. 889
Author(s):  
Anton D. Filev ◽  
Denis N. Silachev ◽  
Ivan A. Ryzhkov ◽  
Konstantin N. Lapin ◽  
Anastasiya S. Babkina ◽  
...  

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.


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