Inflammatory cytokines may mediate hypoxic-ischemic (HI) injury and offer insights into the severity of injury and the timing of recovery. In our randomized, multicenter trial of hypothermia, we analyzed the temporal relationship of serum cytokine levels in neonates with hypoxic-ischemic encephalopathy (HIE) with neurodevelopmental outcome at 12 months. Serum cytokines were measured every 12 hours for 4 days in 28 hypothermic (H) and 22 normothermic (N) neonates with HIE. Monocyte chemotactic protein-1 (MCP-1) and interleukins (IL)-6, IL-8, and IL-10 were significantly higher in the H group. Elevated IL-6 and MCP-1 within 9 hours after birth and low macrophage inflammatory protein 1a (MIP-1a) at 60 to 70 hours of age were associated with death or severely abnormal neurodevelopment at 12 months of age. However, IL-6, IL-8, and MCP-1 showed a biphasic pattern in the H group, with early and delayed peaks. In H neonates with better outcomes, uniform down modulation of IL-6, IL-8, and IL-10 from their peak levels at 24 hours to their nadir at 36 hours was observed. Modulation of serum cytokines after HI injury may be another mechanism of improved outcomes in neonates treated with induced hypothermia.

Our data are consistent with chemokine-associated systemic immunosuppression with hypothermia treatment. In hypothermic neonates, persistence of lower leukocyte counts after rewarming is observed in infants with more severe CNS injury.

Background Delay discounting (DD) is a measure of impulsivity that quantifies preference for a small reward delivered immediately over a large reward delivered after a delay. It has been hypothesized that impulsivity is an endophenotype associated with increased risk for development of alcohol use disorders (AUDs); however, a causal role of impulsivity is difficult to determine with human studies. We tested this hypothesis by assessing the degree of DD present in alcohol-naïve rats selectively bred for either high or low alcohol preference. Methods A novel adaptation of a within-sessions DD procedure was used to compare impulsivity differences between male alcohol-preferring (P) and non-preferring (NP) rat lines (n = 6 per line) using a 5% sucrose reward. Animals chose between two options: 2-sec sipper tube access delivered immediately (small reward) or 8-sec access after a variable delay (large reward). Each 50-min session consisted of 5 blocks of 10 60-sec trials. Within each session, the delay to the large reward increased in each block of trials. Delays were gradually increased over 3 sets to attain a final delay set of 3, 8, 15, 18, and 25 sec. Results Prior to starting delays, there were no significant differences between lines in sucrose consumption or percent choice for the large reward, and both lines exhibited a clear preference for the large reward. After delays were initiated, choice for the large reward decreased as the delay to its presentation increased. Although discounting of the large, delayed reward was observed for both lines, the degree of discounting, or “impulsivity,” was greater for P rats compared with NP rats. Conclusions P rats are more impulsive for sucrose rewards before exposure to alcohol compared with NP rats. Thus, individuals genetically predisposed toward developing AUDs may be more likely to engage in impulsive decision-making prior to alcohol exposure.

Objective:Sex is an important determinant of neonatal outcomes and may have a significant role in the physiologic response to maternal chorioamnionitis. Our goal was to determine cerebral blood flow (CBF) parameters by sex and subsequent neurodevelopment in healthy term infants exposed to chorioamnionitis.Study Design:CBF by Doppler ultrasound in anterior and middle cerebral (ACA, MCA) and basilar arteries were analyzed for time-averaged maximum velocity (TAMX) and corrected resistive index in 52 term control and chorioamnionitis-exposed infants between 24 and 72 h after birth. Placental pathology confirmed histologic evidence of chorioamnionitis (HC). Bayley Scales of Infant Development-III were administered at 12 months.Result:HC male infants had significantly greater TAMX in the MCA and lower mean MCA and ACA resistance than HC females. Abnormal CBF correlated negatively with neurodevelopmental outcome.Conclusion:CBF is altered in term infants with histologically confirmed chorioamnionitis compared with control infants with sex-specific differences.

PURPOSE: To determine specific motor skills in premature infants, match those that correlate with standards tests of motor performance, and MRS measures of abnormal brain biochemistry. METHODS: Prospective cohort study of preterm infants (n = 22). Infant motor assessments were completed at term and 12 weeks corrected gestational age (CGA) using the Test of Infant Motor Performance (TIMP) and Bayley Scales of Infant and Toddler Development-III at 12 months CGA. Infants (n = 12) received MRS scans at term CGA. Rasch analysis and MRS findings investigated TIMP items well targeted to high and low risk infants. RESULTS: A 10 item subset of motor skill items correlated strongly with full 42-item TIMP at term and 12 week testing (r > 0.90, p < 0.001 for both), and with Bayley gross motor scores. MRS metabolites in basal ganglia correlated significantly with both TIMP and 10 item motor tests at term, while frontal white matter metabolites correlated with TIMP and 10 item tests at 12 weeks and Bayley motor scores. CONCLUSION: A short motor skill assessment may be representative of a longer standardized test and relate to brain metabolic function in key areas for motor movement and development. Validation of a shortened assessment may improve early identification of high-risk preterm infants.