Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults

White matter damage (WMD) in preterm neonates is strongly associated with adverse outcome. The etiology of white matter injury is not known but clinical data suggest that ischemia-reperfusion and/or infection-inflammation are important factors. Furthermore, antenatal infection seems to be an important risk factor for brain injury in term infants. In order to explore the pathophysiological mechanisms of WMD and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, numerous novel animal models have been developed over the past decade. WMD can be induced by antenatal or postnatal administration of microbes (E. coli or Gardnerella vaginalis), virus (border disease virus) or bacterial products (lipopolysaccharide, LPS). Alternatively, various hypoperfusion paradigms or administration of excitatory amino acid receptor agonists (excitotoxicity models) can be used. Irrespective of which insult is utilized, the maturational age of the CNS and choice of species seem critical. Generally, lesions with similarity to human WMD, with respect to distribution and morphological characteristics, are easier to induce in gyrencephalic species (rabbits, dogs, cats and sheep) than in rodents. Recently, however, models have been developed in rats (PND 1-7), using either bilateral carotid occlusion or combined hypoxia-ischemia, that produce predominantly white matter lesions. LPS is the infectious agent most often used to produce WMD in immature dogs, cats, or fetal sheep. The mechanism whereby LPS induces brain injury is not completely understood but involves activation of toll-like receptor 4 on immune cells with initiation of a generalized inflammatory response resulting in systemic hypoglycemia, perturbation of coagulation, cerebral hypoperfusion, and activation of inflammatory cells in the CNS. LPS and umbilical cord occlusion both produce WMD with quite similar distribution in 65% gestational sheep. The morphological appearance is different, however, with a more pronounced infiltration of inflammatory cells into the brain and focal microglia/macrophage ("inflammatory WMD") in response to LPS compared to hypoperfusion evoking a more diffuse microglial response usually devoid of cellular infiltrates ("ischemic WMD"). Furthermore, low doses of LPS that by themselves have no adverse effects in 7-day-old rats (maturation corresponding to the near term human fetus), dramatically increase brain injury to a subsequent hypoxic-ischemic challenge, implicating that bacterial products can sensitize the immature CNS. Contrary to this finding, other bacterial agents like lipoteichoic acid were recently shown to induce tolerance of the immature brain suggesting that the innate immune system may respond differently to various ligands, which needs to be further explored.     

Influence of maternal reflective functioning on mothers’ and children's weight: A follow-up study

Based on cross-sectional research linking poor reflective functionining (RF) to eating disorders, the current follow-up study tested whether maternal RF would explain the variance of mothers’ and children's weight beyond the effects of maternal emotional dysregulation. During pregnancy (Time 1 [T1]), 51 women were administered the Difficulties in Emotion Regulation Scale (DERS) and interviewed using the Adult Attachment Interview (AAI). Seven months after delivery (Time 2 [T2]), mother–baby dyads who remained in the study (n = 44) were videotaped (Feeding Scale) during their feeding interaction. Last (Time 3 [T3]), the weight of the 34 children who were still in the study was collected at 3 years of age. Maternal AAI-RF at T1 did not correlate with the DERS at T1 nor with the quality of the feeding interacions at T2. However, it correlated, significantly, with maternal body mass index (BMI) at T1, r = −.298, P = .034, and marginally significantly with baby's BMI at T3, r = −.296, P = .089. Moreover, multiple regression models showed a trend indicating that maternal AAI-RF might explain the variance of mothers’ and children's weight beyond the effects of maternal emotional dysregulation. These findings suggest that working on maternal mentalization might contribute to helping prevent childhood obesity from pregnancy.     

Postural Control Complexity and Fatigue in Minimally Affected Individuals with Multiple Sclerosis

This study investigated changes in postural control complexity in people with multiple sclerosis (PwMS) before and after a fatigue protocol. Thirteen minimally affected PwMS (1.53 ± 1.03- Expanded Disability Status Scale) and 12 non-MS controls. Postural test included quiet stance on a force platform under two visual conditions (saccades and fixation) before and after a fatigue protocol. Postural complexity was assessed through the multiscale entropy. A three-way ANOVA showed a main effect of fatigue in the medial-lateral direction (p <0.007), with fatigue protocol reducing postural complexity in both groups. No differences were found between groups or visual conditions. Minimally affected PwMS demonstrated similar postural complexity compared with non-MS controls under both visual tasks and showed similar decrements in postural complexity as a result of fatigue.     

Religious Involvement and Depression: The Mediating Effect of Relational Spirituality

Journal of Religion and Health - Multiple studies have examined the relationship between religious involvement and depression. Many of these investigations reveal a negative correlation between...     

Affective matching moderates S-R binding

We investigated the moderating influence of affective matching on S-R binding processes in a sequential priming study in which positive and negative nouns had to be categorised as referring to a person or to an object. Irrelevant positive and negative distractor words (adjectives) were integrated with responses into S-R episodes if they had the same valence as the target (affective match condition). In this case, repeating the prime distractor in the probe led to a retrieval of the prime response, which facilitated performance for response repetition sequences but had no effect on performance when responses changed between prime and probe. However, if target and distractor had different valences (affective mismatch condition), no interaction of distractor relation and response relation occurred, indicating that distractors were less likely to be associated with responses into event files during the prime trial episode. Findings reveal that affective mismatches are detected automatically and modulate a binding of irrelevant information with responses.     

Why do the effects of delaying reinforcement in animals and delaying feedback in humans differ? A working-memory analysis

Animal research has shown that reinforcement is substantially less effective when it is delayed, but in studies of human motor learning delays in providing feedback typically have much less effect. One possible explanation is that in human research participants know the response to be learned and can thus focus on it during the delay; that is not the case in experiments on animals. We tested this hypothesis using a task in which participants had minimal information on what movement was correct and found that, as in animal experiments, participants learned only when feedback was immediate. A second experiment confirmed that the effects of the delay depended on how many responses had to be held in working memory: the greater the memory load, the poorer the learning. The results point to the importance of activity during a delay on learning; implications for the teaching of motor skills are discussed.