title: Ameliorative Effects of Antioxidants on the Hippocampal Accumulation of Pathologic Tau in a Rat Model of Blast-Induced Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) can lead to early onset dementia and other related neurodegenerative diseases. We previously demonstrated that damage to the central auditory pathway resulting from blast-induced TBI (bTBI) could be significantly attenuated by a combinatorial antioxidant treatment regimen. In the current study, we examined the localization patterns of normal Tau and the potential blast-induced accumulation of neurotoxic variants of this microtubule-associated protein that are believed to potentiate the neurodegenerative effects associated with synaptic dysfunction in the hippocampus following three successive blast overpressure exposures in nontransgenic rats. We observed a marked increase in the number of both hyperphosphorylated and oligomeric Tau-positive hilar mossy cells and somatic accumulation of endogenous Tau in oligodendrocytes in the hippocampus. Remarkably, a combinatorial regimen of 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) resulted in striking reductions in the numbers of both mossy cells and oligodendrocytes positively labeled for these pathological Tau immunoreactivity patterns in response to bTBI. This treatment strategy represents a promising therapeutic approach for simultaneously reducing or eliminating both primary auditory injury and nonauditory changes associated with bTBI-induced hippocampal neurodegeneration.
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Du
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: West
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA.
authors.forename: Weihua
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Ewert
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Saunders
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Rheal A
authors.initials: RA
authors.lastname: Towner
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Floyd
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA; Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Departments of Physiology and Otolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kopke
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D001753:Blast Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D001557:Benzenesulfonates; D018696:Neuroprotective Agents; D016875:tau Proteins; C120851:disufenton sodium; D000111:Acetylcysteine