Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury

Gajavelli, Shyam; Sinha, Varsha; Mazzeo, Anna Teresa; Spurlock, Markus S.; Lee, Stephanie W.; Ahmed, Aminul I.; Yokobori, Shoji; Bullock, Ross

doi:10.1007/s10863-014-9589-1

Cited by 47 publications

(26 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The initiation of the apoptotic pathway in injured cells is dependent on intracellular ATP concentration (Raghupathi et al, 2000). Previous studies have reported that mitochondrial damage occurs following a TBI event, corresponding with impaired ATP production, increased generation of ROS, and apoptosis (Fischer et al, 2016;Gajavelli et al, 2015;Gilmer, Roberts, Joy, Sullivan, & Scheff, 2009). Rapid mitochondrial ROS formation has been demonstrated in rat brain cells (Jou, Jou, Chen, Lin, & Peng, 2002;Sullivan, Rabchevsky, Waldmeier, & Springer, 2005) and may lead to apoptosis within several minutes to hours (Jou et al, 2004;Nowak et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Pierce

Gupte

Thimmesch

et al. 2018

J of Neuroscience Research

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Pierce

Gupte

Thimmesch

et al. 2018

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…On a broader scale, therapeutic treatment with C-R(7) may have the potential to minimize mitochondrially induced damage resulting from stroke or traumatic brain injury (55,68) and possibly serve to ameliorate slow progressive neurodegenerative disorders such as multiple sclerosis and Parkinson disease (69). Fig.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of N-Methyl-d-aspartate-induced Retinal Neuronal Death by Polyarginine Peptides Is Linked to the Attenuation of Stress-induced Hyperpolarization of the Inner Mitochondrial Membrane Potential

Marshall

Wong

Rupasinghe

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: NMDA receptor hyperactivity results in mitochondrial dysfunction in neurons promoting neurodegenerative disorders. Results: Short polyarginine peptides target mitochondria to promote neuronal survival. Conclusion: Short polyarginine peptides reduce mitochondrial respiration, membrane hyperpolarization, and generation of reactive oxygen species. Significance: Treatment with polyarginine has the potential to minimize neuronal damage resulting from stroke or traumatic brain injury and may be therapeutic to ameliorate multiple sclerosis and Parkinson disease.

show abstract

“…Neuroprotection of CsA is independent of immunosuppression [70]. CsA inhibits the opening of the mitochondrial permeability transition pore and apoptosis [71]. The neuroprotection afforded by CsA dose-dependent in several animal models of TBI, and a therapeutic window exists up to 24 hr post-injury [72].…”

Section: Investigational Drugs Under Early Clinical Trialsmentioning

confidence: 99%

Investigational agents for treatment of traumatic brain injury

Xiong

Zhang

Mahmood

et al. 2015

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

Introduction Traumatic brain injury (TBI) is a major cause of death and disability worldwide. To date, there are no pharmacologic agents proven to improve outcomes from TBI because all the Phase III clinical trials in TBI have failed. Thus, there is a compelling need to develop treatments for TBI. Areas covered The aim of this review is to provide an overview of select cell-based and pharmacological therapies under early development for the treatment of TBI, which seek to enhance cognitive and neurological functional recovery through neuroprotective and neurorestorative strategies. Expert’s opinion TBI elicits both complex degenerative and regenerative tissue responses in the brain. TBI can lead to cognitive, behavioral, and motor deficits. Although numerous promising neuroprotective treatment options have emerged from preclinical studies that mainly target the lesion, translation of preclinical effective neuroprotective drugs to clinical trials has proven challenging. Accumulating evidence indicates that the mammalian brain has a significant, albeit limited, capacity for both structural and functional plasticity as well as regeneration essential for spontaneous functional recovery after injury. A new therapeutic approach is to stimulate neurovascular remodeling by enhancing angiogenesis, neurogenesis, oligodendrogenesis, and axonal sprouting, which in concert, may improve neurological functional recovery after TBI.

show abstract

Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury

Cited by 47 publications

References 154 publications

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Inhibition of N-Methyl-d-aspartate-induced Retinal Neuronal Death by Polyarginine Peptides Is Linked to the Attenuation of Stress-induced Hyperpolarization of the Inner Mitochondrial Membrane Potential

Investigational agents for treatment of traumatic brain injury

Contact Info

Product

Resources

About