Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

Download Full-text

Therapeutic Time Window for Edaravone Treatment of Traumatic Brain Injury in Mice

BioMed Research International ◽

10.1155/2013/379206 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 11

Author(s):

Kazuyuki Miyamoto ◽

Hirokazu Ohtaki ◽

Kenji Dohi ◽

Tomomi Tsumuraya ◽

Dandan Song ◽

...

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Neuronal Death ◽

Time Window ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Therapeutic Time Window

Traumatic brain injury (TBI) is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS) production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI). Edaravone (3.0 mg/kg), or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2∙-) as a marker of ROS, of nitrotyrosine (NT) as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease inO2∙-levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI.

Download Full-text

Reduction of traumatic brain injury-induced cerebral oedema by a free radical scavenger

European Journal of Pharmacology ◽

10.1016/0014-2999(96)00235-x ◽

1996 ◽

Vol 307 (2) ◽

pp. 149-155 ◽

Cited By ~ 30

Author(s):

Margaret A. Petty ◽

Patrick Poulet ◽

Antoine Haas ◽

Izzie J. Namer ◽

Joseph Wagner

Keyword(s):

Traumatic Brain Injury ◽

Free Radical ◽

Brain Injury ◽

Cerebral Oedema ◽

Free Radical Scavenger ◽

Radical Scavenger

Download Full-text

A-107 Quantifying the Effect of Sleepiness and Mood on Gross Neuropsychological Functioning in a Forensic Population with a History of Traumatic Brain Injury

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.125 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1156-1156

Author(s):

Sarka T Brown ◽

Kimberly Gorgens ◽

Marybeth Lehto ◽

Laura Meyer ◽

Gina Signoracci

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Cognitive Performance ◽

Test Performance ◽

Neuropsychological Functioning ◽

Negative Mood ◽

Mood States ◽

Health Concern ◽

Forensic Population ◽

History Of

Abstract Objective Traumatic brain injury (TBI) is a serious public health concern. Furthermore, inmates and probationers are at a higher risk for TBI, as well as mental health issues and sleepiness. Both sleep and mood disturbance have been linked to poor cognitive performance. These state-dependent cognitive changes can undermine the evaluation of true cognitive ability and contaminate validity. This study examined the effects of sleep and mood on neurocognitive functioning and its impact on the validity of assessment results. Methods This study looked at retrospective Automated Neuropsychological Assessment Metrics (ANAM) core battery data. The sample included inmates and probationers (n = 419) with a history of TBI. A multiple linear regression was used to examine the relationship between self-reported sleepiness, mood state, and cognitive performance. Results All regression models were statistically significant, with negative mood being the most significant predictor of ANAM throughput scores (p = 0.000). Higher endorsement of negative mood states was related to lower cognitive performance overall (p = 0.003). Sleepiness predicted worse performance on at the end of the battery (p < 0.05), whereas positive mood predicted better performance at the beginning of the battery (p < 0.01). Conslusion The present study confirms that negative mood adversely affects global neurocognitive test performance in a forensic population. Examiners should be aware that sleepiness and mood states have an effect on test performance during even brief cognitive batteries. The current findings suggest that it is imperative to screen and identify sleepiness and negative mood symptoms as they may depress test results and threaten the validity or test interpretations and recommendations.

Download Full-text

The Novel Free Radical Scavenger, Edaravone, Increases Neural Stem Cell Number Around the Area of Damage Following Rat Traumatic Brain Injury

Neurotoxicity Research ◽

10.1007/s12640-009-9081-6 ◽

2009 ◽

Vol 16 (4) ◽

pp. 378-389 ◽

Cited By ~ 31

Author(s):

Tatsuki Itoh ◽

Takao Satou ◽

Shozo Nishida ◽

Masahiro Tsubaki ◽

Shigeo Hashimoto ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Stem Cell ◽

Free Radical ◽

Brain Injury ◽

Neural Stem Cell ◽

Cell Number ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

The Novel

Download Full-text

The Nitrone Free Radical Scavenger NXY-059 Is Neuroprotective when Administered after Traumatic Brain Injury in the Rat

Journal of Neurotrauma ◽

10.1089/neu.2008.0585 ◽

2008 ◽

Vol 25 (12) ◽

pp. 1449-1457 ◽

Cited By ~ 21

Author(s):

Fredrik Clausen ◽

Niklas Marklund ◽

Anders Lewén ◽

Lars Hillered

Keyword(s):

Traumatic Brain Injury ◽

Free Radical ◽

Brain Injury ◽

Free Radical Scavenger ◽

Radical Scavenger

Download Full-text

Neuroprotective effect of hydrogen sulfide against glutamate-induced oxidative stress is mediated via the p53/glutaminase 2 pathway after traumatic brain injury

Aging ◽

10.18632/aging.202575 ◽

2021 ◽

Vol 13 (5) ◽

pp. 7180-7189

Author(s):

Jianping Sun ◽

Xiaoyu Li ◽

Xiaoyu Gu ◽

Hailong Du ◽

Gengshen Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Hydrogen Sulfide ◽

Brain Injury ◽

Neuroprotective Effect

Download Full-text

Protective Effect of Diphenhydramine against Traumatic Brain Injury in Rats via Modulation of Oxidative Stress and Inflammation

Pharmacology ◽

10.1159/000502767 ◽

2019 ◽

Vol 105 (1-2) ◽

pp. 47-53 ◽

Cited By ~ 2

Author(s):

Wenyong Pan ◽

Zhigang Cao ◽

Dongyang Liu ◽

Yingbin Jiao

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Protective Effect ◽

Neuronal Degeneration ◽

Neuroprotective Effect ◽

B Cell Lymphoma ◽

Treated Group ◽

Dependent Manner ◽

And Oxidative Stress

Background: Traumatic brain injury (TBI) is considered a major burden across the globe affecting both individuals and their families. Therefore, the present study was conducted to determine the protective effect of diphenhydramine (DPM) against TBI in experimental rats. Methods: The effect of DPM was evaluated on the cerebral edema (CE) and neuronal degeneration after the induction of experimental brain injury in rats. The effect of DPM was also investigated on the inflammatory cytokines, for example, tumor necrosis factor-α and interleukin 1β and oxidative stress markers, such as malondialdehyde, superoxide dismutase, and glutathione peroxidase. Western blot analysis was used to investigate the effect of DPM on B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cleaved caspase-3. Results: Results of the study suggest that DPM causes reduction in CE and prevents neuronal degeneration. It also causes reduction in inflammation and oxidative stress in a dose-dependent manner. The level of Bax was found to be elevated, together with reduction in the Bcl-2 level in the DPM-treated group. Conclusion: DPM exerts a neuroprotective effect after TBI via the attenuation of oxidative stress, inflammation, and mitochondrial apoptosis pathways.

Download Full-text

Traumatic Brain Injury Altered Normal Brain Signaling Pathways: Implications for Novel Therapeutics Approaches

Current Neuropharmacology ◽

10.2174/1570159x16666180911121847 ◽

2019 ◽

Vol 17 (7) ◽

pp. 614-629 ◽

Cited By ~ 2

Author(s):

Arti Rana ◽

Shamsher Singh ◽

Ruchika Sharma ◽

Anoop Kumar

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Alzheimer Disease ◽

Signaling Pathways ◽

Neurological Disorders ◽

Normal Brain ◽

Therapeutic Approaches ◽

Ionic Imbalance ◽

The Brain

Traumatic brain injury (TBI) is the main reason of lifelong disability and casualty worldwide. In the United State alone, 1.7 million traumatic events occur yearly, out of which 50,000 results in deaths. Injury to the brain could alter various biological signaling pathways such as excitotoxicity, ionic imbalance, oxidative stress, inflammation, and apoptosis which can result in various neurological disorders such as Psychosis, Depression, Alzheimer disease, Parkinson disease, etc. In literature, various reports have indicated the alteration of these pathways after traumatic brain injury but the exact mechanism is still unclear. Thus, in the first part of this article, we have tried to summarize TBI as a modulator of various neuronal signaling pathways. Currently, very few drugs are available in the market for the treatment of TBI and these drugs only provide the supportive care. Thus, in the second part of the article, based on TBI altered signaling pathways, we have tried to find out potential targets and promising therapeutic approaches in the treatment of TBI.

Download Full-text