title: Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration-grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3 h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24 h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3 h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24 h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored.
authors.affiliation: 1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.|2 Departments of Cellular and Structure Biology, University of Texas Health Science Center , San Antonio, Texas.|3 Department of Neurology, University of Texas Health Science Center , San Antonio, Texas.
authors.forename: Lora
authors.initials: L
authors.lastname: Talley Watts
authors.affiliation: 1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.
authors.forename: Justin Alexander
authors.initials: JA
authors.lastname: Long
authors.affiliation: 1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.
authors.forename: Robert Cole
authors.initials: RC
authors.lastname: Boggs
authors.affiliation: 1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.
authors.forename: Hemanth
authors.initials: H
authors.lastname: Manga
authors.affiliation: 1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Huang
authors.affiliation: 1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.affiliation: 1 Research Imaging Institute, University of Texas Health Science Center , San Antonio, Texas.|3 Department of Neurology, University of Texas Health Science Center , San Antonio, Texas.|4 Department of Ophthalmology, University of Texas Health Science Center , San Antonio, Texas.|5 Research Division, South Texas Veterans Health Care System , San Antonio, Texas.
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005552:Forelimb; D008279:Magnetic Resonance Imaging; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000293:injuries*
chemical_list: D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D008751:Methylene Blue
keywords: CCI; MRI; TBI; behavioral outcomes; methylene blue; mitochondria