title: Prolonged hippocampal cell death following closed-head traumatic brain injury in rats.
abstract: Traumatic brain injury (TBI) leads to enduring cognitive disorders. Although recent evidence has shown that controlled cortical impact in a rodent may induce memory deficits with prolonged cell death in the dentate gyrus (DG) of the hippocampus, few studies have reported long-term chronic hippocampal cell death following 'closed-head' TBI (cTBI), the predominant form of human TBI. Therefore, the aim of this study was to quantify terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)(+) apoptotic hippocampal cells as well as hippocampal cells with hallmark morphological features of degenerating cells in a chronic setting of cTBI in rats. TUNEL assays and Cresyl violet staining were performed using 6-month post-TBI fixed hippocampal sections. Evidence of prolonged hippocampal cell death was shown by the presence of a significantly increased number of TUNEL(+) cells in the cornu ammonis 1-3 (CA1-CA3) and DG of the hippocampus compared with intact controls. In addition, Cresyl violet staining indicated a significantly elevated number of cells with the degenerative morphological features in all hippocampal subregions (CA1-CA3, hilus, and DG). These results suggest that prolonged cell death may occur in multiple regions of the hippocampus following cTBI.
authors.affiliation: aBrain Rehabilitation Research Center of Excellence, Malcom Randall VA Medical Center, North Florida/South Georgia Veterans Health System bDepartment of Physiological Sciences, College of Veterinary Medicine Departments of cNeuroscience dNeurology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Tsuda
authors.forename: Jiamei
authors.initials: J
authors.lastname: Hou
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Nelson
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Wilkie
authors.forename: Golam
authors.initials: G
authors.lastname: Mustafa
authors.forename: Ankita
authors.initials: A
authors.lastname: Sinharoy
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Watts
authors.forename: Floyd J
authors.initials: FJ
authors.lastname: Thompson
authors.forename: Prodip K
authors.initials: PK
authors.lastname: Bose
mesh_terms: D000818:Animals; D017209:Apoptosis; D000070642:Brain Injuries, Traumatic / Q000473:pathology*; D016923:Cell Death; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D017207:Rats, Sprague-Dawley