Biology subjects

Gorman-Sandler, E.

Publications and source records attributed to Gorman-Sandler, E..

2 recordsLinked to original sources

bioRxiv2026

Pediatric traumatic brain injury elicits acute neuroinflammation and long-term changes in social, cognitive, and decision-making behaviors in male and female rats

Traumatic brain injury (TBI) is one of the leading causes of emergency room visits in children under 10. Children are potentially more vulnerable to the adverse effects of TBI, given that their brains are still developing at the time of injury. Indeed, early life TBI has been linked to cognitive, social, and mood-related impairments later in life. The neuroimmune system has been implicated in adult TBI mechanisms and plays numerous key roles in brain development, making it an interesting candidate for linking pediatric TBI and prolonged behavioral alterations. Here we establish a rat model of mild pediatric TBI to investigate the relationship between early life TBI, acute responses of neuroimmune cells, and chronic behavioral dysregulation. At postnatal day 15, which is roughly equivalent to toddler age, male and female rat pups received a TBI via lateral fluid percussion injury. At 3 days post injury, TBI increased microglia and astrocyte coverage locally in the Perilesional Cortex but not in more distant corticolimbic regions. However, the hippocampus and prefrontal cortex did exhibit increased expression of the phagocytic marker CD68 in microglia, suggesting widespread glial activation even in the absence of gross coverage change. TBI also impacted mast cells, early-response innate immune cells, increasing their number and degranulation in multiple regions. In the juvenile and early adult periods, TBI impaired cognitive function, reduced sociability, and increased avoidance, with no change in anxiety-like behavior. Later in adulthood, TBI continued to impact cognitive behavior, increasing risky decision-making and impairing optimization months after injury. Together, these results suggest that pediatric TBI causes lasting cognitive and social dysregulation, possibly via acute neuroimmune alterations following injury at a critical period of brain development.

neuroscience↗

bioRxiv2022

Gestational stress decreases postpartum mitochondrial respiration in the prefrontal cortex of female rats

Postpartum depression (PPD) is a major psychiatric complication of childbirth, affecting up to 20% of mothers, yet remains understudied. Mitochondria, dynamic organelles crucial for cell homeostasis and energy production, share links with many of the proposed mechanisms underlying PPD pathology. Brain mitochondrial function is affected by stress, a major risk factor for development of PPD, and is linked to anxiety-like and social behaviors. Considering the importance of mitochondria in regulating brain function and behavior, we hypothesized that mitochondrial dysfunction is associated with behavioral alterations in a chronic stress-induced rat model of PPD. Using a validated and translationally relevant chronic mild unpredictable stress paradigm during late gestation, we induced PPD-relevant behaviors in adult postpartum Wistar rats. In the mid-postpartum, we measured mitochondrial function in the prefrontal cortex (PFC) and nucleus accumbens (NAc) using high-resolution respirometry. We then measured protein expression of mitochondrial complex proteins and 4-hydroxynonenal (a marker of oxidative stress), and Th1/Th2 cytokine levels in PFC and plasma. We report novel findings that gestational stress decreased mitochondrial function in the PFC, but not the NAc of postpartum dams. However, in groups controlling for the effects of either stress or parity alone, no differences in mitochondrial respiration measured in either brain regions were observed compared to nulliparous controls. This decrease in PFC mitochondrial function in stressed dams was accompanied by negative behavioral consequences in the postpartum, complex-I specific deficits in protein expression, and increased Tumor Necrosis Factor alpha cytokine levels in plasma and PFC. Overall, we report an association between PFC mitochondrial respiration, PPD-relevant behaviors, and inflammation following gestational stress, highlighting a potential role for mitochondrial function in postpartum health.

neuroscience↗