title: Neurologic impairment following closed head injury predicts post-traumatic neurogenesis.
abstract: In the mammalian hippocampus, neurogenesis persists into adulthood, and increased generation of newborn neurons could be of clinical benefit following concussive head injuries. Post-traumatic neurogenesis has been well documented using "open" traumatic brain injury (TBI) models in rodents; however, human TBI most commonly involves closed head injury. Here we used a closed head injury (CHI) model to examine post-traumatic hippocampal neurogenesis in mice. All mice were subjected to the same CHI protocol, and a gross-motor based injury severity score was used to characterize neurologic impairment 1h after the injury. When analyzed 2weeks later, post-traumatic neurogenesis was significantly increased only in mice with a high degree of transient neurologic impairment immediately after injury. This increase was associated with an early increase in c-fos activity, and subsequent reactive astrocytosis and microglial activation in the dentate gyrus. Our results demonstrate that the initial degree of neurologic impairment after closed head injury predicts the induction of secondary physiologic and pathophysiologic processes, and that animals with severe neurologic impairment early after injury manifest an increase in post-traumatic neurogenesis in the absence of gross anatomic pathology.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, OHSU, 3181 S.W. Sam Jackson Park Road, Mail Code UHT, Portland, OR 97239, United States.
authors.forename: L E
authors.initials: LE
authors.lastname: Villasana
authors.affiliation: The Vollum Institute, OHSU, 3181 S.W. Sam Jackson Park Road, Mail Code L474, Portland OR 97239, United States.
authors.forename: G L
authors.initials: GL
authors.lastname: Westbrook
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, OHSU, 3181 S.W. Sam Jackson Park Road, Mail Code UHT, Portland, OR 97239, United States; Portland VA Medical Center, 3710 S.W. U.S. VA Hospital Road, Mail Code P3ANES, Portland, OR 97239, United States. Electronic address: schneler@ohsu.edu.
authors.forename: E
authors.initials: E
authors.lastname: Schnell
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005260:Female; D037502:Galectin 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016489:Head Injuries, Closed / Q000150:complications* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000209:etiology*; D055495:Neurogenesis / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D000089622:Doublecortin Domain Proteins; D037502:Galectin 3; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D001973:Bromodeoxyuridine
keywords: Adult neurogenesis; Closed head injury; Hippocampus; Neurologic severity score; Traumatic brain injury