Biology subjects

Martens, K. M.

Publications and source records attributed to Martens, K. M..

3 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↗

bioRxiv2026

Frontal Brain Injury Reduces Sensitivity to Reward-Predictive Cues and Remodels the Nucleus Accumbens

Traumatic brain injuries (TBIs) are more than mere lesions and generate a persistent secondary pathology. This, combined with functional reorganization of circuits post-injury, may explain the increased risk for psychiatric disorders in patients with TBI. In the current studies, we demonstrate that frontal TBI changed the Pavlovian behavioral response to reinforcer-predicting cues and reduced the motivational value of cues. TBI also chronically impaired decision-making on a gambling-like task with reinforcer-paired cues. To investigate how these changes occur, we evaluated the nucleus accumbens (NAc) core. At a subacute time point (14 days), we confirmed reduced input to the NAc with optogenetics and evaluated electrophysiological and transcriptional changes. TBI increased neuronal excitability and the single nucleus RNA sequencing profile indicated a substantial stress and inflammatory response, but also high indicators of plasticity, particularly in D1- and D2-positive medium spiny neurons. To evaluate how these subacute changes transitioned to chronic NAc dysfunction, we measured immunohistochemical surrogates of activity post-mortem and recorded calcium activity from the NAc after TBI during Pavlovian conditioning. TBI reduced histological markers of activity and reduced cue-evoked calcium activity. Overall, these data indicate that substantial reorganization of the NAc occurs following frontal brain injury. A primary effect of this is to reduce the salience of environmental cues linked to outcomes. The inability to properly process outcomes could contribute to broader psychiatric symptoms after TBI, including impairments in decision-making, behavioral flexibility, and impulsivity but also presents a potential treatment target.

neuroscience↗

bioRxiv2025

Caloric restriction worsens decision-making impairments and gut dysbiosis after brain injury in male rats

Traumatic brain injury (TBI) causes long-term deficits in decision-making and disrupts the gut microbiome. Dysbiosis of the gut microbiome is a potential contributor to the development of multiple psychiatric and neurological disorders and may be a contributor to chronic symptoms from TBI. Caloric restriction is often used to assess psychiatric-related behaviors in animals, but also affects the gut microbiome. In the current study, we evaluated the effects of caloric restriction versus free feeding on a frontal controlled cortical impact TBI. Rats were trained on the rodent gambling task, an analog of the Iowa gambling task, to assess risk-based decision-making. The microbiome was sampled through the acute to subacute period post-injury and lesion size and microglia counts evaluated at 10 weeks post-injury. Caloric restriction did not affect decision-making at baseline, but did affect motivational variables. TBI impaired decision-making and this effect was exacerbated by caloric restriction. Other motivation-related variables followed a similar pattern of impairment with TBI driving impairments that were worsened by caloric restriction. The gut microbiome was initially dysbiotic, but largely recovered within 14 days post-injury. Despite this, acute gut measurements were predictive of chronic decision-making impairment. These data indicate a role for the gut microbiome in the evolution of TBI deficits and suggest that interventions targeting the gut may have a limited window of opportunity to treat long-term deficits.

neuroscience↗