title: Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury.
abstract: OBJECTIVE
  With the recent increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions), several models of rmTBI have been established. Characterizing these models in terms of behavioral and histopathological outcomes is vital to assess their clinical translatability. The purpose of this study is to provide an in-depth behavioral and histopathological phenotype of a clinically relevant model of rmTBI.
  
  
  METHODS
  The authors used a previously published weight-drop model of rmTBI (7 injuries in 9 days) in 2- to 3-month-old mice that produces cognitive deficits without persistent loss of consciousness, seizures, gross structural imaging findings, or microscopic evidence of structural brain damage. Injured and sham-injured (anesthesia only) mice were subjected to a battery of behavioral testing, including tests of balance (rotarod), spatial memory (Morris water maze), anxiety (open field plus maze), and exploratory behavior (hole-board test). After behavioral testing, brains were assessed for histopathological outcomes, including brain volume and microglial and astrocyte immunolabeling.
  
  
  RESULTS
  Compared with sham-injured mice, mice subjected to rmTBI showed increased exploratory behavior and had impaired balance and worse spatial memory that persisted up to 3 months after injury. Long-term behavioral deficits were associated with chronic increased astrocytosis and microgliosis but no volume changes.
  
  
  CONCLUSIONS
  The authors demonstrate that their rmTBI model results in a characteristic behavioral phenotype that correlates with the clinical syndrome of concussion and repetitive concussion. This model offers a platform from which to study therapeutic interventions for rmTBI.
authors.affiliation: Division of Emergency Medicine.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Mannix
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Berglass
authors.forename: Justin
authors.initials: J
authors.lastname: Berkner
authors.forename: Philippe
authors.initials: P
authors.lastname: Moleus
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qiu
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.forename: Georgia
authors.initials: G
authors.lastname: Gunner
authors.forename: Laura
authors.initials: L
authors.lastname: Berglass
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Jantzie
authors.forename: Shenandoah
authors.initials: S
authors.lastname: Robinson
authors.forename: William P
authors.initials: WP
authors.lastname: Meehan
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology; D001253:Astrocytes / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology*; D001924:Brain Concussion / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005911:Gliosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D006222:Hamartoma / Q000473:pathology; D016142:Holoprosencephaly / Q000473:pathology; D007027:Hypothalamic Diseases / Q000473:pathology; D008168:Lung / Q000002:abnormalities / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008810:Mice, Inbred C57BL; D008850:Microphthalmos / Q000473:pathology; D009043:Motor Activity / Q000502:physiology; D009095:Mullerian Ducts / Q000002:abnormalities / Q000473:pathology; D011884:Radius / Q000002:abnormalities / Q000473:pathology; D011897:Random Allocation; D065853:Spatial Learning / Q000502:physiology; D015599:Trauma Severity Indices; D014474:Unconsciousness / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
keywords: CTE = chronic traumatic encephalopathy; LOC = loss of consciousness; MWM = Morris water maze; ROI = region of interest; behavior; closed head injury; concussion; gliosis; rmTBI = repetitive mild traumatic brain injury; traumatic brain injury