Mitoquinone Helps Combat the Neurological, Cognitive, and Molecular Consequences of Open Head Traumatic Brain Injury at Chronic Time Point
Muhammad Ali Haidar,
Zaynab Shakkour,
Chloe Barsa,
Maha Tabet,
Sarin Mekhjian,
Hala Darwish,
Mona Goli,
Deborah Shear,
Jignesh D. Pandya,
Yehia Mechref,
Riyad El Khoury,
Kevin Wang,
Firas Kobeissy
Affiliations
Muhammad Ali Haidar
Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon
Zaynab Shakkour
Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA
Chloe Barsa
Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon
Maha Tabet
Centre de Biologie Integrative (CBI), Molecular, Cellular, and Developmental Biology Department (MCD), University of Toulouse, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), 31062 Toulouse, France
Sarin Mekhjian
Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon
Hala Darwish
Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon
Mona Goli
Chemistry and Bioehcmistry Department, Texas Tech University, Lubbock, TX 79409, USA
Deborah Shear
Brain Trauma Neuroprotection (BTN) Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Jignesh D. Pandya
Brain Trauma Neuroprotection (BTN) Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Yehia Mechref
Chemistry and Bioehcmistry Department, Texas Tech University, Lubbock, TX 79409, USA
Riyad El Khoury
Neuromuscular Diagnostic Laboratory, Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon
Kevin Wang
Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, FL 32611, USA
Firas Kobeissy
Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon
Traumatic brain injury (TBI) is a heterogeneous disease in its origin, neuropathology, and prognosis, with no FDA-approved treatments. The pathology of TBI is complicated and not sufficiently understood, which is the reason why more than 30 clinical trials in the past three decades turned out unsuccessful in phase III. The multifaceted pathophysiology of TBI involves a cascade of metabolic and molecular events including inflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. In this study, an open head TBI mouse model, induced by controlled cortical impact (CCI), was used to investigate the chronic protective effects of mitoquinone (MitoQ) administration 30 days post-injury. Neurological functions were assessed with the Garcia neuroscore, pole climbing, grip strength, and adhesive removal tests, whereas cognitive and behavioral functions were assessed using the object recognition, Morris water maze, and forced swim tests. As for molecular effects, immunofluorescence staining was conducted to investigate microgliosis, astrocytosis, neuronal cell count, and axonal integrity. The results show that MitoQ enhanced neurological and cognitive functions 30 days post-injury. MitoQ also decreased the activation of astrocytes and microglia, which was accompanied by improved axonal integrity and neuronal cell count in the cortex. Therefore, we conclude that MitoQ has neuroprotective effects in a moderate open head CCI mouse model by decreasing oxidative stress, neuroinflammation, and axonal injury.
