Mice Born to Mothers with Gravida Traumatic Brain Injury Have Distorted Brain Circuitry and Altered Immune Responses

Maha Saber, J. Bryce Ortiz, Luisa M.Rojas Valencia, Xiaokuang Ma, Bret R. Tallent, P. David Adelson, Rachel K. Rowe, Shenfeng Qiu, Jonathan Lifshitz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Intimate partner violence (IPV) increases risk of traumatic brain injury (TBI). Physical assaults increase in frequency and intensity during pregnancy. The consequences of TBI during pregnancy (gravida TBI; gTBI) on offspring development is unknown, for which stress and inflammation during pregnancy worsen fetal developmental outcomes. We hypothesized that gTBI would lead to increased anxiety- and depression-related behavior, altered inflammatory responses and gut pathology, and distorted brain circuitry in mixed-sex offspring compared to mice born to control mothers. Pregnant dams received either diffuse TBI or sham injury (control) 12 days post-coitum. We found that male gTBI offspring were principal drivers of the gTBI effects on health, physiology, and behavior. For example, male, but not female, gTBI offspring weighed significantly less at weaning compared to male control offspring. At post-natal day (PND) 28, gTBI offspring had significantly weaker intralaminar connectivity onto layer 5 pre-frontal pyramidal neurons compared to control offspring. Neurological performance on anxiety-like behaviors was decreased, with only marginal differences in depressive-like behaviors, for gTBI offspring compared to control offspring. At PND42 and PND58, circulating neutrophil and monocyte populations were significantly smaller in gTBI male offspring than control male offspring. In response to a subsequent inflammatory challenge at PND75, gTBI offspring had significantly smaller circulating neutrophil populations than control offspring. Anxiety-like behaviors persisted during the immune challenge in gTBI offspring. However, spleen immune response and gut histology showed no significant differences between groups. The results compel further studies to determine the full extent of gTBI on fetal and maternal outcomes.

Original languageEnglish (US)
Pages (from-to)2862-2880
Number of pages19
JournalJournal of Neurotrauma
Volume38
Issue number20
DOIs
StatePublished - Oct 15 2021

Keywords

  • circuit connectivity
  • fetal development
  • gestational injury
  • immune response
  • intimate partner violence
  • maternal brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint

Dive into the research topics of 'Mice Born to Mothers with Gravida Traumatic Brain Injury Have Distorted Brain Circuitry and Altered Immune Responses'. Together they form a unique fingerprint.

Cite this