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Updated: Jul 4, 2025
Detecting Behavioral Deficits in Rats After Traumatic Brain Injury
Published on: January 30, 2018
Neurobehavioral Abnormalities in Offspring of Young Adult Male Rats With a History of Traumatic Brain Injury
Ling-Sha Ju1, Jiepei Zhu1, Timothy E Morey1
1Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida, USA.
Insights
Offspring of fathers with traumatic brain injury (TBI) exhibit sex-dependent neurobehavioral abnormalities, even without direct contact. This suggests TBI can impact offspring development through non-social pathways, highlighting potential intergenerational effects.
Area of Science:
- Neuroscience
- Neurobiology
- Behavioral Science
Background:
- Children of parents with traumatic brain injury (TBI) show increased risk for psychiatric disorders.
- This association is often linked to parental psychological changes and altered family environments.
- The study investigates potential TBI-induced neurodevelopmental effects on offspring independent of social contact.
Purpose of the Study:
- To test if offspring of male rats with TBI develop neurodevelopmental abnormalities.
- To assess these abnormalities in the absence of direct social interaction with the TBI-affected sire.
- To examine sex-specific effects in the offspring's neurobehavioral development.
Main Methods:
- Male Sprague-Dawley rats (F0) underwent moderate TBI via fluid percussion injury under sevoflurane anesthesia.
- Control F0 rats experienced a sham procedure.
- F0 rats were mated to produce F1 offspring, which were then behaviorally tested (anxiety, sensory gating, spatial memory) and analyzed for neurobiological markers (gene expression, HPA axis, inflammation).
Main Results:
- Acutely, TBI sires showed altered gene expression related to chloride transport and glucocorticoid receptors, increased corticosterone, and heightened inflammation markers in the brain.
- Long-term, TBI sires displayed anxiety, impaired sensory-motor gating, and spatial memory deficits.
- F1 male offspring exhibited widespread neurobehavioral abnormalities and altered gene expression, while F1 females showed deficits primarily in sensory-motor gating, with more profound inflammatory changes.
Conclusions:
- Moderate TBI in male rats can lead to sex-dependent neurobehavioral abnormalities in their offspring.
- These effects occur without direct social contact, suggesting non-social intergenerational transmission of TBI-induced changes.
- Findings highlight the importance of considering paternal TBI history in offspring neurodevelopmental outcomes.
Abstract:
Children of parents with traumatic brain injury (TBI) are more likely to develop psychiatric disorders. This association is usually attributed to TBI-induced changes in parents' personality and families' social environment. We tested the hypothesis that offspring of young adult male rats with TBI develop neurodevelopmental abnormalities in the absence of direct social contact with sires. Male Sprague-Dawley rats (F0 generation) in the TBI group underwent moderate TBI via a midline fluid percussion injury that involved craniectomy under sevoflurane (SEVO) anesthesia for 40 min on post-natal Day 60 (P60), while F0 rats in the control group were placed in a new cage, one per cage, for the equivalent time duration. A subset of F0 rats was sacrificed on P66 to assess acute changes in hypothalamic-pituitary-adrenal (HPA) axis and inflammation markers. The remaining F0 males were mated with naive females on P90 to generate offspring (F1 generation). The F0 males and F1 males and females were sequentially evaluated in the elevated plus maze, for pre-pulse inhibition of acoustic startle, in the Morris water maze, and for resting and stress levels of serum corticosterone starting on ∼P105 (F0) and ∼P60 (F1), followed by tissue collection for further analyses. Acutely, the F0 TBI males had messenger RNA (mRNA) transcripts altered to support an increased hypothalamic and hippocampal Na+-K+-Cl- (Slc12a2) Cl- importer / K+-2Cl- (Slc12a5) Cl- exporter ratio and decreased hippocampal glucocorticoid receptors (Nr3c1), as well as increased serum levels of corticosterone, interleukin-1β (IL-1β), and biomarkers of activated hippocampal microglia and astrocytes. Long-term, F0 TBI rats exhibited increased corticosterone concentrations at rest and under stress, anxiety-like behavior, impaired sensory-motor gating, and impaired spatial memory. These abnormalities were underpinned by reduced mRNA levels of hypothalamic and hippocampal mineralocorticoid receptors (Nr3c2), hippocampal Nr3c1, and hypothalamic brain-derived neurotrophic factor (Bdnf), as well as elevated serum levels of IL-1β, and biomarkers of activated hippocampal microglia and astrocytes. F1 male offspring of TBI sires exhibited abnormalities in all behavioral tests, while their F1 female counterparts had abnormal pre-pulse inhibition responses only. F1 male offspring of TBI sires also had reduced mRNA levels of hippocampal Nr3c1 and Nr3c2, as well as hypothalamic and hippocampal Bdnf, whereas increases in inflammatory markers were more profound in F1 females. These findings suggest that offspring of sires with a history of a moderate TBI that involved craniectomy under SEVO anesthesia for 40 min, develop sex-dependent neurobehavioral abnormalities in the absence of direct social interaction between the sire and the offspring.
