PMID- 35203460 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220301 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 10 IP - 2 DP - 2022 Jan 24 TI - Mitoquinone Helps Combat the Neurological, Cognitive, and Molecular Consequences of Open Head Traumatic Brain Injury at Chronic Time Point. LID - 10.3390/biomedicines10020250 [doi] LID - 250 AB - 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. FAU - Haidar, Muhammad Ali AU - Haidar MA AUID- ORCID: 0000-0002-0236-1526 AD - Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon. FAU - Shakkour, Zaynab AU - Shakkour Z AD - Department of Pathology & Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, USA. FAU - Barsa, Chloe AU - Barsa C AD - Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon. FAU - Tabet, Maha AU - Tabet M AD - Centre de Biologie Integrative (CBI), Molecular, Cellular, and Developmental Biology Department (MCD), University of Toulouse, Centre National de la Recherche Scientifique (CNRS), Universite Paul Sabatier (UPS), 31062 Toulouse, France. FAU - Mekhjian, Sarin AU - Mekhjian S AD - Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon. FAU - Darwish, Hala AU - Darwish H AD - Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon. FAU - Goli, Mona AU - Goli M AD - Chemistry and Bioehcmistry Department, Texas Tech University, Lubbock, TX 79409, USA. FAU - Shear, Deborah AU - Shear D AD - Brain Trauma Neuroprotection (BTN) Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Pandya, Jignesh D AU - Pandya JD AD - Brain Trauma Neuroprotection (BTN) Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. FAU - Mechref, Yehia AU - Mechref Y AUID- ORCID: 0000-0002-6661-6073 AD - Chemistry and Bioehcmistry Department, Texas Tech University, Lubbock, TX 79409, USA. FAU - El Khoury, Riyad AU - El Khoury R AUID- ORCID: 0000-0001-8386-4629 AD - Neuromuscular Diagnostic Laboratory, Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon. FAU - Wang, Kevin AU - Wang K AD - Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, FL 32611, USA. FAU - Kobeissy, Firas AU - Kobeissy F AUID- ORCID: 0000-0002-5008-6944 AD - Faculty of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon. AD - Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, FL 32611, USA. LA - eng PT - Journal Article DEP - 20220124 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC8869514 OTO - NOTNLM OT - moderate traumatic brain injury OT - neurodegeneration OT - neuroinflammation OT - neurotrauma OT - oxidative stress COIS- The authors declare no conflict of interest. EDAT- 2022/02/26 06:00 MHDA- 2022/02/26 06:01 PMCR- 2022/01/24 CRDT- 2022/02/25 01:01 PHST- 2021/12/22 00:00 [received] PHST- 2022/01/15 00:00 [revised] PHST- 2022/01/17 00:00 [accepted] PHST- 2022/02/25 01:01 [entrez] PHST- 2022/02/26 06:00 [pubmed] PHST- 2022/02/26 06:01 [medline] PHST- 2022/01/24 00:00 [pmc-release] AID - biomedicines10020250 [pii] AID - biomedicines-10-00250 [pii] AID - 10.3390/biomedicines10020250 [doi] PST - epublish SO - Biomedicines. 2022 Jan 24;10(2):250. doi: 10.3390/biomedicines10020250.