Reward and immune responses in adolescent females following experimental traumatic brain injury

Cannella, Lee Anne; Andrews, Allison M.; Razmpour, Roshanak; McGary, Hannah; Corbett, Cali; Kahn, Johannes; Ramirez, Servio H.

doi:10.1016/j.bbr.2019.112333

Cited by 6 publications

(6 citation statements)

References 43 publications

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“…The influence of biological sex after TBI is epitomized by the observation that males and females have different rates of post-traumatic drug and alcohol disorders [4,84,85]. Consistent with these clinical data, males and females perform differently in CPP after TBI [31,32,86]. Females are more susceptible to addiction and drug-related effects than males [87], both in humans [88,89] and in rodent models [90,91].…”

Section: Discussionmentioning

confidence: 82%

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Sex-Specific and Traumatic Brain Injury Effects on Dopamine Receptor Expression in the Hippocampus

Iannucci,

O’Neill,

Wang

et al. 2023

IJMS

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Traumatic brain injury (TBI) is a major health concern. Each year, over 50 million individuals worldwide suffer from TBI, and this leads to a number of acute and chronic health issues. These include affective and cognitive impairment, as well as an increased risk of alcohol and drug use. The dopaminergic system, a key component of reward circuitry, has been linked to alcohol and other substance use disorders, and previous research indicates that TBI can induce plasticity within this system. Understanding how TBI modifies the dopaminergic system may offer insights into the heightened substance use and reward-seeking behavior following TBI. The hippocampus, a critical component of the reward circuit, is responsible for encoding and integrating the spatial and salient aspects of rewarding stimuli. This study explored TBI-related changes in neuronal D2 receptor expression within the hippocampus, examining the hypothesis that sex differences exist in both baseline hippocampal D2 receptor expression and its response to TBI. Utilizing D2-expressing tdTomato transgenic male and female mice, we implemented either a sham injury or the lateral fluid percussion injury (FPI) model of TBI and subsequently performed a region-specific quantification of D2 expression in the hippocampus. The results show that male mice exhibit higher baseline hippocampal D2 expression compared to female mice. Additionally, there was a significant interaction effect between sex and injury on the expression of D2 in the hippocampus, particularly in regions of the dentate gyrus. Furthermore, TBI led to significant reductions in hippocampal D2 expression in male mice, while female mice remained mostly unaffected. These results suggest that hippocampal D2 expression varies between male and female mice, with the female dopaminergic system demonstrating less susceptibility to TBI-induced plasticity.

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Section: Discussionmentioning

confidence: 82%

“…Importantly, TBI alters drug-induced CPP [28,29]. Sex differences in CPP, including after TBI, have also been identified [30][31][32]. Thus, it is important to describe both biological sex-and TBI-related effects on dopaminergic circuitry in the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Sex-Specific and Traumatic Brain Injury Effects on Dopamine Receptor Expression in the Hippocampus

Iannucci,

O’Neill,

Wang

et al. 2023

IJMS

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“…In an adult mouse study using CCI, resident microglia are increased 7 days post-injury in the cortex [7]. Similarly, adult mouse CCI shows increases in microglia on the ipsilateral side of the brain at 2-and 14-days post-injury with parallel increases in PSD95 + immature microglia at 2 days, suggesting a de novo birth and maturation of resident microglia [17]. Using Marmarou's weight drop model, Balb/c mice show macrophage increases at 1-, 2-, and 3-days post-injury, whereas microglia in the brain dramatically decrease [8].…”

Section: Discussionmentioning

confidence: 87%

Cerebral and Peripheral Immune Cell Changes following Rodent Juvenile Traumatic Brain Injury

Smith,

Taylor,

Brooks

et al. 2024

Brain Sciences

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Traumatic brain injury (TBI) is one of the leading causes of death and disability. TBI is associated with neuroinflammation, but temporal changes in immune and inflammatory signaling following TBI have not been fully elucidated. Furthermore, there have been no previous studies on changes in immune cell populations following TBI via the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA). The current study aimed to determine the time course changes to inflammatory marker mRNA expression in the acute period following TBI in juvenile rats and to determine acute changes to brain and circulating immune cell populations. For this study, post-natal day (PND)-30 male Long Evans rats sustained a TBI or Sham TBI and were euthanized at 0, 3, 6, 12, 24, or 96 h post-injury. Prefrontal cortex and hippocampus samples were used to determine mRNA expression changes of inflammatory factors. The mRNA expression of the pro-inflammatory cytokine TNF-α was significantly elevated at 6 h post-injury in both regions evaluated. To evaluate immune cell populations, male Long Evans rats were euthanized at 48 h post-injury, and brain and blood samples were used for cell sorting by marker-specific antibodies. In the peripheral blood, there was an elevation in CD3+ total T cells, CD45R+ total B cells, and CD3+CD4+ helper T cells in the TBI subjects. However, there were no changes to natural killer cells or CD3+CD8+ cytotoxic T cell populations. In the brain, there was a reduction in CD11b/c+ monocytes/macrophages, but no changes in other immune cell populations. At 48 h post-injury, the TBI subjects also demonstrated expansion of the thymic medulla. These changes in the cerebral and blood immune cell populations and thymic medulla expansion may implicate the subacute recovery timeframe as a vulnerable window for the immune system in the pediatric population.

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“…Importantly, the experience of TBI has been shown to be both an outcome and predictor of disordered substance use (Graham & Cardon, 2008; West, 2011). Recent studies have shown TBI status appears to sensitize reward processing to cocaine in rodents (Cannella et al, 2019), as well as alter neural systems related to reward in people who experienced a TBI early in life, which may contribute to disordered substance use (Cannella et al, 20199). Specific to cannabis, TBI status may influence motivations to use cannabis; one study found that individuals with at least moderate-to-severe TBI reported using cannabis after their TBI, in part, as a way to cope with ongoing stress or anxiety (Hawley et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Impact of acute stress on neural indices of positive and negative reinforcement processing in cannabis users.

Preston¹,

Albanese²,

Schmidt³

et al. 2022

Psychology of Addictive Behaviors

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Objective: Chronic cannabis use is maintained in part through dysregulated stress and reward response systems. Specifically, stress-related negative affect is thought to act as a salient motivator for chronic substance use. Models of addiction posit that the transition from positive to negative reinforcement motives for substance use is a key mechanism of disordered use. However, research in substance-using samples has not assessed stress-related neural processing of both positive and negative reinforcement. Method: Therefore, the present study utilized laboratory stress induction to examine how stress affects the reward positivity, an event-related potential sensitive to both positive (RewP) and negative (relief-RewP) reinforcement, in 87 cannabis users (58.10% female, M age = 19.40) varying in cannabis use disorder (CUD) severity and, as part of larger study aims, history of traumatic brain injury (TBI). We predicted greater CUD severity would be associated with a blunted RewP and enhanced relief-RewP, particularly after stress induction, independent of TBI status. Results: Findings indicated that CUD severity was not associated with RewP/relief-RewP amplitude regardless of acute stress. Exploratory analyses revealed, however, that among those with history of TBI+, CUD severity was associated with greater stress-elicited blunting of the RewP and enhancement of the relief-RewP. Conclusion: Although initial findings contradict current allostatic models of addiction, exploratory findings suggest that history of TBI, and potentially other confounding variables related to increased risk of TBI experience, may influence the extent to which stressful experiences modulate the neurophysiology of both positive and negative reinforcement reward processing in CUD. Public Health Significance StatementThe present study suggests that in people with history of TBI, greater disordered cannabis use is associated with a stress-elicited decrease in reward sensitivity to positive reinforcement, in addition to a simultaneous increase in sensitivity to negative reinforcement. Present results may inform future interventions targeting reward dysregulation in specific populations of disordered cannabis users.

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Reward and immune responses in adolescent females following experimental traumatic brain injury

Cited by 6 publications

References 43 publications

Sex-Specific and Traumatic Brain Injury Effects on Dopamine Receptor Expression in the Hippocampus

Sex-Specific and Traumatic Brain Injury Effects on Dopamine Receptor Expression in the Hippocampus

Cerebral and Peripheral Immune Cell Changes following Rodent Juvenile Traumatic Brain Injury

Impact of acute stress on neural indices of positive and negative reinforcement processing in cannabis users.

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