ubiquinone and Brain-Injuries--Traumatic

Traumatic brain injury (TBI) is a major cause of disability and death. Mild TBI (mTBI) constitutes ~75% of all TBI cases. Repeated exposure to mTBI (rmTBI), leads to the exacerbation of the symptoms compared to single mTBI. To date, there is no FDA-approved drug for TBI or rmTBI. This research aims to investigate possible rmTBI neurotherapy by targeting TBI pathology-related mechanisms. Oxidative stress is partly responsible for TBI/rmTBI neuropathologic outcomes. Thus, targeting oxidative stress may ameliorate TBI/rmTBI consequences. In this study, we hypothesized that mitoquinone (MitoQ), a mitochondria-targeted antioxidant, would ameliorate TBI/rmTBI associated pathologic features by mitigating rmTBI-induced oxidative stress. To model rmTBI, C57BL/6 mice were subjected to three concussive head injuries. MitoQ (5 mg/kg) was administered intraperitoneally to rmTBI+MitoQ mice twice per week over one month. Behavioral and cognitive outcomes were assessed, 30 days following the first head injury, using a battery of behavioral tests. Immunofluorescence was used to assess neuroinflammation and neuronal integrity. Also, qRT-PCR was used to evaluate the expression levels of antioxidant enzymes. Our findings indicated that MitoQ alleviated fine motor function and learning impairments caused by rmTBI. Mechanistically, MitoQ reduced astrocytosis, microgliosis, dendritic and axonal shearing, and increased the expression of antioxidant enzymes. MitoQ administration following rmTBI may represent an efficient approach to ameliorate rmTBI neurological and cellular outcomes with no observable side effects.

Topics: Animals; Antioxidants; Brain Concussion; Brain Injuries, Traumatic; Dietary Supplements; Disease Models, Animal; Mice; Mice, Inbred C57BL; Organophosphorus Compounds; Oxidative Stress; Ubiquinone

The objective of this review is to map evidence on coenzyme Q10 (CoQ10) use in traumatic brain injury (TBI).. Traumatic brain injury is an insult to the brain structure caused by external force and resulting in physiological disruption to brain function. Globally, 60% of all TBIs occur from road traffic accidents. In 2016, the World Health Organization reported that road traffic accidents were among the top 10 leading causes of death. Following the initial brain injury, a secondary injury can occur due primarily to a significant increase in production of free radicals causing oxidative stress, which can dictate the patient's ability to survive. Coenzyme Q10 is known to protect neuronal cells from oxidative stress; the mechanism for this has been examined in studies using rats. This review will examine what is known about CoQ10 in TBI and identify gaps in the literature, which may guide future research.. The review will include both human and animal subjects who have experienced a TBI in the acute/laboratory-controlled setting and where CoQ10 is supplemented. Animal studies will be included. The review will consider experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies, and interrupted time-series studies. Studies published in English will be considered, with no date restriction.. Searches will be conducted in the Cochrane Library, MEDLINE, Embase, CINAHL and trial registries. Data will be extracted and presented on details about the population, concept, context, study methods and key findings.

Topics: Brain; Brain Injuries, Traumatic; Clinical Trials as Topic; Dietary Supplements; Female; Humans; Male; Oxidative Stress; Research Design; Review Literature as Topic; Treatment Outcome; Ubiquinone; Vitamins

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.

Topics: Animals; Apoptosis; Brain Injuries, Traumatic; Glial Fibrillary Acidic Protein; Male; Mitochondria; Random Allocation; Rats; Rats, Inbred F344; Ubiquinone; Ubiquitin Thiolesterase