title: Exercise preconditioning improves traumatic brain injury outcomes.
abstract: OBJECTIVE
  To determine whether 6 weeks of exercise performed prior to traumatic brain injury (TBI) could improve post-TBI behavioral outcomes in mice, and if exercise increases neuroprotective molecules (vascular endothelial growth factor-A [VEGF-A], erythropoietin [EPO], and heme oxygenase-1 [HO-1]) in brain regions responsible for movement (sensorimotor cortex) and memory (hippocampus).
  
  
  METHODS
  120 mice were randomly assigned to one of four groups: (1) no exercise+no TBI (NOEX-NOTBI [n=30]), (2) no exercise+TBI (NOEX-TBI [n=30]), (3) exercise+no TBI (EX-NOTBI [n=30]), and (4) exercise+TBI (EX-TBI [n=30]). The gridwalk task and radial arm water maze were used to evaluate sensorimotor and cognitive function, respectively. Quantitative real time polymerase chain reaction and immunostaining were performed to investigate VEGF-A, EPO, and HO-1 mRNA and protein expression in the right cerebral cortex and ipsilateral hippocampus.
  
  
  RESULTS
  EX-TBI mice displayed reduced post-TBI sensorimotor and cognitive deficits when compared to NOEX-TBI mice. EX-NOTBI and EX-TBI mice showed elevated VEGF-A and EPO mRNA in the cortex and hippocampus, and increased VEGF-A and EPO staining of sensorimotor cortex neurons 1 day post-TBI and/or post-exercise. EX-TBI mice also exhibited increased VEGF-A staining of hippocampal neurons 1 day post-TBI/post-exercise. NOEX-TBI mice demonstrated increased HO-1 mRNA in the cortex (3 days post-TBI) and hippocampus (3 and 7 days post-TBI), but HO-1 was not increased in mice that exercised.
  
  
  CONCLUSIONS
  Improved TBI outcomes following exercise preconditioning are associated with increased expression of specific neuroprotective genes and proteins (VEGF-A and EPO, but not HO-1) in the brain.
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Taylor
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Montgomery
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Gregory
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: NBERMAN@kumc.edu.
authors.forename: Nancy E J
authors.initials: NE
authors.lastname: Berman
mesh_terms: D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D003071:Cognition / Q000502:physiology; D004921:Erythropoietin / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function; D066191:Sensorimotor Cortex / Q000473:pathology / Q000503:physiopathology*; D012720:Severity of Illness Index; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D004921:Erythropoietin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Cognitive function; Erythropoietin; Exercise; Sensorimotor function; Traumatic brain injury; Vascular endothelial growth factor