title: Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.
abstract: Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed cell proliferation may evolve into more severe neurodegenerative diseases and psychiatric disorders currently being recognized in traumatized TBI patients.
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Acosta
authors.affiliation: James A. Haley Veterans Affairs Medical Center, Tampa, Florida, United States of America ; Department of Psychology, Center for Preclinical & Clinical Research on PTSD, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Diamond
authors.affiliation: James A. Haley Veterans Affairs Medical Center, Tampa, Florida, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Wolfe
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shinozuka
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Diana G
authors.initials: DG
authors.lastname: Hernandez
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America ; Office of Research and Innovation, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, United States of America.
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019394:Ki-67 Antigen / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C000714328:DCX protein, human; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides