Antenatal Magnesium Sulfate Benefits Female Preterm Infants but Results in Poor Male Outcomes.

Magnesium sulfate (MagSul) is used clinically to prevent eclamptic seizures during pregnancy and as a tocolytic for preterm labor. More recently, it has been implicated as offering neural protection in utero for at-risk infants. However, evidence is mixed. Some studies found that MagSul reduced the incidence of cerebral palsy (CP) but did not improve other measures of neurologic function. Others did not find any improvement in outcomes. Inconsistencies in the literature may reflect the fact that sex effects are largely ignored, despite evidence that MagSul shows sex effects in animal models of neonatal brain injury. The current study used retrospective infant data to assess differences in developmental outcomes as a function of sex and MagSul treatment. We found that on 18-month neurodevelopmental cognitive and language measures, preterm males treated with MagSul (n = 209) had significantly worse scores than their untreated counterparts (n = 135; p < 0.05). Female preterm infants treated with MagSul (n = 220), on the other hand, showed a cognitive benefit relative to untreated females (n = 123; p < 0.05). No significant effects of MagSul were seen among females on language (p > 0.05). These results have tremendous implications for risk-benefit considerations in the ongoing use of MagSul and may explain why benefits have been hard to identify in clinical trials when sex is not considered.

A novel approach to the assessment of higher-order rule learning in male mice.

Historically, the development of valid and reliable methods for assessing higher-order cognitive abilities (e.g., rule learning and transfer) has been difficult in rodent models. To date, limited evidence supports the existence of higher cognitive abilities such as rule generation and complex decision-making in mice, rats, and rabbits. To this end, we sought to develop a task that would require mice to learn and transfer a rule. We trained mice to visually discriminate a series of images (image set, six total) of increasing complexity following three stages: (1) learn a visual target, (2) learn a rule (ignore any new images around the target), and finally (3) apply this rule in abstract form to a comparable but new image set. To evaluate learning for each stage, we measured (1) days (and performance by day) to discriminate the original target at criterion, (2) days (and performance by day) to get back to criterion when images in the set were altered by the introduction of distractors (rule learning), and (3) overall days (and performance by day) to criterion when experienced versus naïve cohorts of mice were tested on the same image set (rule transfer). Twenty-seven wild-type male C57 mice were tested using Bussey-Saksida touchscreen operant conditioning boxes (Lafayette Instruments). Two comparable black-white image sets were delivered sequentially (counterbalanced for order) to two identical cohorts of mice. Results showed that all mice were able to effectively learn their initial target image and could recall it >80 d later. We also found that mice were able to quickly learn and apply a "rule" : Ignore new distractors and continue to identify their visual target embedded in more complex images. The presence of rule learning was supported because performance criterion thresholds were regained much faster than initial learning when distractors were introduced. On the other hand, mice appeared unable to transfer this rule to a new set of stimuli. This is supported because visual discrimination curves for a new image set were no better than an initial (naïve) learning by a matched cohort of mice. Overall results have important implications for phenotyping research and particularly for the modeling of complex disorders in mice.