New method to induce mild traumatic brain injury in rodents produces differential outcomes in female and male Sprague Dawley rats

J Neurosci Methods. 2017 Oct 1:290:133-144. doi: 10.1016/j.jneumeth.2017.07.030. Epub 2017 Aug 2.

Abstract

Background: Mild traumatic brain injuries (mTBI) are an increasing health concern due to persistent behavioral and neurological effects. To better understand these effects, researchers frequently rely on animal injury models. Existing models, however, may not adequately reproduce the mechanism of injury as it occurs in humans.

New method: Our new model for inducing mTBI in rodents entails acceleration of the animal toward a stationary impact zone to produce rapid rotational movement of the head. The aim of the present experiment was to characterize the effects of this injury in female and male rats on behavior, cognition, and neural plasticity.

Results: mTBI produced the most widespread effects in females: they were more active during recovery within minutes of mTBI and more active in the center of the open field 4days after mTBI. Spatial learning deficits in the water maze were mild but persistent and accompanied by reduced numbers of immature neurons in the hippocampus along with reductions in sera levels of the neurotrophin, BDNF. By contrast, male mTBI rats mainly exhibited mild spatial learning deficits, with no other observed effects.

Comparison with existing methods: Our model induced effects on behavior and biology in rats that aligned with existing models. However, new patterns were observed, particularly when comparing females and males.

Conclusions: Taken together, these findings confirm the validity of this model and point to key differences between females and males in symptom severity and type. Additionally, our model adds a novel injury mechanism that complements existing rodent models.

Keywords: Adult hippocampal neurogenesis; BDNF; Behavioral inhibition; Biological sex differences; Spatial cognition.

MeSH terms

  • Animals
  • Anxiety / etiology
  • Brain Concussion* / classification
  • Brain Concussion* / etiology
  • Brain Concussion* / pathology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Disease Models, Animal*
  • Doublecortin Domain Proteins
  • Exploratory Behavior / physiology
  • Female
  • Gene Expression Regulation / physiology
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Male
  • Maze Learning / physiology
  • Memory Disorders / etiology
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / physiology*
  • Neuropeptides / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / physiology
  • Sex Characteristics*
  • Statistics, Nonparametric

Substances

  • Brain-Derived Neurotrophic Factor
  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides