Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal–microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal–microglial signaling. Quantification of apoptotic debris in fractalkine-knockout (KO) and CX3CR1-KO mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a “find-me” signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-KO and CX3CR1-KO mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these KOs by 6 h after ethanol treatment. Collectively, this suggests that fractalkine acts as a “find me” signal released by apoptotic neurons, and subsequently plays a critical role in modulating both clearance and inflammatory cytokine gene expression after ethanol-induced apoptosis.

Conditional stimuli (CS) that are paired with reward can be used to motivate instrumental responses. This process is called Pavlovian-instrumental transfer (PIT). A recent study in rats suggested that habitual responses are particularly sensitive to the motivational effects of reward cues. The current experiments examined this idea using ratio and interval training in mice. Two groups of animals were trained to lever press for food pellets that were delivered on random ratio or random interval schedules. Devaluation tests revealed that interval training led to habitual responding while ratio training produced goal-directed actions. The presentation of CSs paired with reward led to positive transfer in both groups, however, the size of this effect was much larger in mice that were trained on interval schedules. This result suggests that habitual responses are more sensitive to the motivational influence of reward cues than goal-directed actions. The implications for neurobiological models of motivation and drug seeking behaviors are discussed.

Objective: This study investigated patient outcomes of care before and after transitioning to a surgical intensivist-led trauma-intensive care unit (ICU) team. The intensivist team provided daily multidisciplinary rounds and continuity of care. Prior to an intensivist model, general surgeons cared for trauma patients admitted to the unit. Methods: Outcomes of 1,078 trauma patients, admitted to the ICU at a Level II trauma center, under care of general surgeons (1/2011-8/2012, n = 449) were retrospectively compared with care managed by a surgical intensivist team (1/2013-5/2015, n = 629) by Pearson Chi-squared and Wilcoxon tests. A multivariable logistic regression technique was used to control for covariates. Demographics and injury severity were analyzed. The primary outcome was ICU mortality. The secondary outcomes were length of stay (LOS), ventilator-free and ICU-free days, and ICU readmission rate. Other data collected included palliative care consultation. Results: There were no statistically significant differences in ICU mortality (P = 0.055), hospital LOS (P = 0.481), ventilator-free days (P = 0.174), or ICU readmission rate (P = 0.587). The surgical intensivist team consulted palliative care more frequently (4.0% vs 13.5%, P < 0.001), while managing more trauma patients who were older than 65 years (P < 0.001) with lower Glasgow Coma Scale (P = 0.048) and higher injury severity (P = 0.025) and abbreviated injury scale (P < 0.001) scores. Discussion: There were no differences in outcomes. However, incorporating palliative care consultation in the ICU is essential in the support of critically ill patients and their families. These data demonstrate that a surgical intensivist team utilized palliative care more often in the management of trauma patients admitted to the ICU.