Acute gut microbiome changes after traumatic brain injury are associated with chronic deficits in decision-making and impulsivity in male rats.

The mechanisms underlying chronic psychiatric-like impairments after traumatic brain injury (TBI) are currently unknown. The goal of the present study was to assess the role of diet and the gut microbiome in psychiatric symptoms after TBI. Rats were randomly assigned to receive a high-fat diet (HFD) or calorie-matched low-fat diet (LFD). After 2 weeks of free access, rats began training on the rodent gambling task (RGT), a measure of risky decision-making and motor impulsivity. After training, rats received a bilateral frontal TBI or a sham procedure and continued postinjury testing for 10 weeks. Fecal samples were collected before injury and 3-, 30-, and 60 days postinjury to evaluate the gut microbiome. HFD altered the microbiome, but ultimately had low-magnitude effects on behavior and did not modify functional outcomes after TBI. Injury-induced functional deficits were far more robust; TBI substantially decreased optimal choice and increased suboptimal choice and motor impulsivity on the RGT. TBI also affected the microbiome, and a model comparison approach revealed that bacterial diversity measured 3 days postinjury was predictive of chronic psychiatric-like deficits on the RGT. A functional metagenomic analysis identified changes to dopamine and serotonin synthesis pathways as a potential candidate mechanism. Thus, the gut may be a potential acute treatment target for psychiatric symptoms after TBI, as well as a biomarker for injury and deficit severity. However, further research will be needed to confirm and extend these findings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Chronic lipopolysaccharide impairs motivation when delivered to the ventricles, but not when delivered peripherally in male rats.

Increased neuroinflammation relative to controls is observed in major depression. Moreover, depressive disorders are significantly elevated in conditions which increase neuroinflammation (e.g., brain injury, Parkinson's disease, Alzheimer's disease). To better understand the relationship between neuroinflammation and depression, additional research is needed. The current set of studies made use of the progressive ratio (PR) task in male rats, a stable measure of motivation which can be evaluated daily and thus is ideally suited for examining a potential role for chronic neuroinflammation in depressive-like behavior. Lipopolysaccharide (LPS) was used to induce an inflammatory response. Experiment 1 confirmed prior acute LPS administration experiments for sensitivity of the PR task, with a large effect at 2 mg/kg, a partial effect at 1 mg/kg, and no effect at 0.5 mg/kg. Experiment 2 evaluated a dose-response of continuous s.c. LPS infusion but found no significant elevation in brain cytokines after 14 days at any doses of 0.1, 0.5, 1, or 2 mg/kg/week. Experiment 3 assessed motivation during continuous s.c. infusion of a large 5 mg/kg/week LPS dose and found no significant impairments in motivation, but transient decreases in rates of lever pressing (i.e., only motoric deficits). Experiment 4 measured motivation during continuous ICV infusion of 10.5 µg/kg/week LPS and found significantly decreased motivation without changes to rates of lever pressing (i.e., only motivational deficits). Together these results suggest that the PR task is efficient for evaluating models of chronic inflammation, and that the adaptive response to chronic LPS exposure, even when delivered centrally, may necessitate alternative strategies for generating long-term neuroinflammation.

Unilateral parietal brain injury increases risk-taking on a rat gambling task.

Traumatic brain injury (TBI) affects millions of individuals every year. Many of these injuries lead to lasting effects, particularly impairments in domains broadly classified as executive functions, such as impulse control and decision-making. While these impairments have been historically associated with frontal brain damage, other injuries such as concussion or parietal injury also contribute to similar dysfunction. However, it is unknown whether animal models of TBI would replicate these broad effects that are observed in human patients. In the current study, we delivered a unilateral parietal controlled cortical impact injury and assessed the performance of rats on a motoric task (rotarod) and a test of decision-making and impulsivity (rodent gambling task). TBI rats demonstrated significant motor impairments on the rotarod task; however, this did not extend to difficulties inhibiting motor actions (impulsivity). In addition, TBI caused chronic alterations to risk-based decision-making, extending out to 12 weeks post-injury. Specifically, rats with TBI preferred the riskiest, and most suboptimal option over all others. The current data suggest that models of unilateral TBI are sufficient for replicating some aspects of executive dysfunction (risky decision-making), while others are limited to frontal damage (impulsivity). These models may be used to develop therapeutics targeted at the chronic post-injury period when these symptoms often manifest in patients, a critically understudied area in preclinical TBI research.

Cathodal Transcranial Direct-Current Stimulation Selectively Decreases Impulsivity after Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) often results in chronic psychiatric-like symptoms. In a condition with few therapeutic options, neuromodulation has emerged as a promising potential treatment avenue for these individuals. The goal of the current study was to determine if transcranial direct-current stimulation (tDCS) could treat deficits of impulsivity and attention in rats. This could then be used as a model to investigate treatment parameters and the mechanism of action underlying therapeutic effects. Rats were trained on a task to measure attention and motor impulsivity (five-choice serial reaction time task), then given a frontal, controlled cortical impact injury. After rats recovered to a new baseline, tDCS (cathodal, 10 min, 800 µA) was delivered daily prior to testing in a counterbalanced, cross-over design. Treatment with tDCS selectively reduced impulsivity in the TBI group, and the greatest recovery occurred in the rats with the largest deficits. With these data, we have established a rat model for studying the effects of tDCS on psychiatric-like dysfunction. More research is needed to determine the mechanism of action by which tDCS-related gains occur.