Citation

Sanchez CM, Titus DJ, Wilson NM, Freund JE, Atkins CM. J. Neurotrauma 2020; ePub(ePub): ePub.

Copyright

(Copyright © 2020, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2020.7267

PMID

32862765

Abstract

The neurocognitive impairments associated with mild traumatic brain injury (TBI) often resolve within 1-2 weeks, however, a subset of people exhibit persistent cognitive dysfunction for weeks to months after injury. The factors that contribute to these persistent deficits are unknown. One potential risk factor for worsened outcome after TBI is a history of stress experienced by a person early in life. Early life stress (ELS) includes maltreatment such as neglect and interferes with the normal construction of cortical and hippocampal circuits. We hypothesized that a history of ELS contributes to persistent learning and memory dysfunction following a TBI. To explore this interaction, we modeled ELS by separating Sprague Dawley pups from their nursing mothers from postnatal days 2-14 for 3 hr daily. At 2 months of age, male rats received sham surgery or mild to moderate parasagittal fluid-percussion brain injury. We found that the combination of ELS with TBI in adulthood impaired hippocampal-dependent learning, as assessed with contextual fear conditioning, the water maze task, and spatial working memory. Cortical atrophy was significantly exacerbated in TBI animals exposed to ELS as compared to normal-reared TBI animals. Changes in corticosterone in response to restraint stress were prolonged in TBI animals that received ELS as compared to TBI animals that were normally reared or sham animals that received ELS. Our findings indicate that ELS is a risk factor for worsened outcome after TBI and results in persistent learning and memory deficits, worsened cortical pathology, and an exacerbation of the hormonal stress response.

Language: en

Keywords

TRAUMATIC BRAIN INJURY; LEARNING AND MEMORY; BEHAVIORAL ASSESSMENTS