title: Posttraumatic hypothermia increases doublecortin expressing neurons in the dentate gyrus after traumatic brain injury in the rat.
abstract: Previous studies have demonstrated that moderate hypothermia reduces histopathological damage and improves behavioral outcome after experimental traumatic brain injury (TBI). Further investigations have clarified the mechanisms underlying the beneficial effects of hypothermia by showing that cooling reduces multiple cell injury cascades. The purpose of this study was to determine whether hypothermia could also enhance endogenous reparative processes following TBI such as neurogenesis and the replacement of lost neurons. Male Sprague-Dawley rats underwent moderate fluid-percussion brain injury and then were randomized into normothermia (37°C) or hypothermia (33°C) treatment. Animals received injections of 5-bromo-2'-deoxyuridine (BrdU) to detect mitotic cells after brain injury. After 3 or 7 days, animals were perfusion-fixed and processed for immunocytochemistry and confocal analysis. Sections were stained for markers selective for cell proliferation (BrdU), neuroblasts and immature neurons (doublecortin), and mature neurons (NeuN) and then analyzed using non-biased stereology to quantify neurogenesis in the dentate gyrus (DG). At 7 days after TBI, both normothermic and hypothermic TBI animals demonstrated a significant increase in the number of BrdU-immunoreactive cells in the DG as compared to sham-operated controls. At 7 days post-injury, hypothermia animals had a greater number of BrdU (ipsilateral cortex) and doublecortin (ipsilateral and contralateral cortex) immunoreactive cells in the DG as compared to normothermia animals. Because adult neurogenesis following injury may be associated with enhanced functional recovery, these data demonstrate that therapeutic hypothermia sustains the increase in neurogenesis induced by TBI and this may be one of the mechanisms by which hypothermia promotes reparative strategies in the injured nervous system.
authors.affiliation: Department of Neurological Surgery, The Neurotrauma Research Center, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Amade
authors.initials: A
authors.lastname: Bregy
authors.forename: Ryan
authors.initials: R
authors.lastname: Nixon
authors.forename: George
authors.initials: G
authors.lastname: Lotocki
authors.forename: Ofelia F
authors.initials: OF
authors.lastname: Alonso
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Atkins
authors.forename: Pantelis
authors.initials: P
authors.lastname: Tsoulfas
authors.forename: Helen M
authors.initials: HM
authors.lastname: Bramlett
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation; D007036:Hypothermia, Induced / Q000379:methods; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides