Delayed and Abbreviated Environmental Enrichment after Brain Trauma Promotes Motor and Cognitive Recovery That Is Not Contingent on Increased Neurogenesis

J Neurotrauma. 2019 Mar 1;36(5):756-767. doi: 10.1089/neu.2018.5866. Epub 2018 Nov 28.

Abstract

Environmental enrichment (EE) confers motor and cognitive recovery in pre-clinical models of traumatic brain injury (TBI), and neurogenesis has been attributed to mediating the benefits. Whether that ascription is correct has not been fully investigated. Hence, the goal of the current study is to further clarify the possible role of learning-induced hippocampal neurogenesis on functional recovery after cortical impact or sham injury by utilizing two EE paradigms (i.e., early + continuous, initiated immediately after TBI and presented 24 h/day; and delayed + abbreviated, initiated 4 days after TBI for 6 h/day) and comparing them to one another as well as to standard (STD) housed controls. Motor and cognitive performance was assessed on post-operative Days 1-5 and 14-19, respectively, for the STD and early + continuous EE groups and on Days 4-8 and 17-22, for the delayed + abbreviated EE groups. Rats were injected with bromodeoxyuridine (BrdU, 500 mg/ kg; intraperitoneally) for 3 days (12 h apart) before cognitive training and sacrificed 1 week later for quantification of BrdU+ and doublecortin (DCX+) labeled cells. Both early + continuous and delayed + abbreviated EE promoted motor and cognitive recovery after TBI, relative to STD (p < 0.05), and did not differ from one another (p > 0.05). However, only early + continuous EE increased DCX+ cells beyond the level of STD-housed controls (p < 0.05). No effect of EE on non-injured controls was observed. Based on these data, two novel conclusions emerged. First, EE does not need to be provided early and continuously after TBI to confer benefits, which lends credence to the delayed + abbreviated EE paradigm as a relevant pre-clinical model of neurorehabilitation. Second, the functional recovery observed after TBI in the delayed + abbreviated EE paradigm is not contingent on increased hippocampal neurogenesis. Future studies will elucidate alternate viable mechanisms mediating the benefits induced by EE.

Keywords: Morris water maze; behavioral outcome; controlled cortical impact; environmental enrichment; functional recovery; learning and memory; traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / physiopathology
  • Brain Injuries, Traumatic / rehabilitation*
  • Doublecortin Protein
  • Hippocampus / physiopathology
  • Housing, Animal*
  • Male
  • Neurogenesis*
  • Neurological Rehabilitation / methods
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function*
  • Social Environment*