Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes.

Adverse neurodevelopmental outcomes are linked to perinatal production of inflammatory mediators, including interleukin 6 (IL-6). While a pivotal role for maternal elevation in IL-6 has been established in determining neurobehavioral outcomes in the offspring and considered the primary target mediating the fetal inflammatory response, questions remain as to the specific actions of IL-6 on the developing brain. CD-1 male mice received a subdural injection of the bioactive fusion protein, hyper IL-6 (HIL-6) on postnatal-day (PND)4 and assessed from preweaning until adulthood. Immunohistochemical evaluation of astrocytes and microglia and mRNA levels for pro-inflammatory cytokines and host response genes indicated no evidence of an acute neuroinflammatory injury response. HIL-6 accelerated motor development and increased reactivity to stimulation and number of entries in a light/dark chamber, decreased ability to learn to withhold a response in passive avoidance, and effected deficits in social novelty behavior. No changes were observed in motor activity, pre-pulse startle inhibition, or learning and memory in the Morris water maze or radial arm maze, as have been reported for models of more severe developmental neuroinflammation. In young animals, mRNA levels for MBP and PLP/DM20 decreased and less complexity of MBP processes in the cortex was evident by immunohistochemistry. The non-hydroxy cerebroside fraction of cerebral lipids was increased. These results provide evidence for selective effects of IL-6 signaling, particularly trans-signaling, in the developing brain in the absence of a general neuroinflammatory response. These data contribute to our further understanding of the multiple aspects of IL-6 signaling in the developing brain.

Review of the evidence for treatment of children with autism with selective serotonin reuptake inhibitors.

PURPOSE: To review the potential role of serotonin dysregulation in autism and the efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating core deficits and associated symptoms of autism in children. The literature was searched for reports of SSRI use in children with autism. Data are presented from prospective clinical trials that evaluated treatment outcomes. CONCLUSIONS: Some SSRIs show moderate success in managing specific behaviors. Only fluoxetine shows evidence of decreasing global autism severity. PRACTICE IMPLICATION: Definitive conclusions concerning selection criteria, dosage, safety, and efficacy cannot be drawn given the current state of evidence.

Diffuse white matter injury and neurologic outcomes of infants born very preterm in the 1990s.

Neurocognitive outcomes of infants born very preterm (less than 32 weeks gestation) remain a major concern in perinatal practice. Very preterm birth rates have increased, with enhanced survival since 1990. As focal brain lesions become less common, diffuse injury to both gray and white matter is now the primary focus for improving neurologic outcomes in survivors. Recent evidence supports preoligodendrocytes as the principal cellular target of diffuse white matter injury due to their susceptibility to hypoxic-ischemic and inflammatory insults. An understanding of their development and vulnerability can inform acute nursing care of very preterm infants.

Maternal infection and white matter toxicity.

Studies examining maternal infection as a risk factor for neurological disorders in the offspring have suggested that altered maternal immune status during pregnancy can be considered as an adverse event in prenatal development. Infection occurring in the mother during the gestational period has been implicated in multiple neurological effects. The current manuscript will consider the issue of immune/inflammatory conditions during prenatal development where adverse outcomes have been linked to maternal systemic infection. The discussions will focus primary on white matter and oligodendrocytes as they have been identified as target processes. This white matter damage occurs in very early preterm infants and in various other human diseases currently being examined for a linkage to maternal or early developmental immune status. The intent is to draw attention to the impact of altered immune status during pregnancy on the offspring for the consideration of such contributing factors to the general assessment of developmental neurotoxicology.

Carbon monoxide neurotoxicity: transient inhibition of avoidance response and delayed microglia reaction in the absence of neuronal death.

Carbon monoxide exposure produces neurobehavioral effects associated with the level of carboxyhemoglobin (COHb) in the blood. A threshold has been proposed of approximately 35% COHb for the manifestation of disruption in neurobehavioral tasks. The effects of CO exposure producing 30-40% carboxyhemoglobin (COHb) levels in young adult male Fischer 344 rats were examined with regard to clinical signs of toxicity, performance on a previously learned avoidance procedure, and neuronal and glia histopathology. High levels of exposure (4000 ppm) for 15 min were imposed on either a background blood COHb level of 5% produced by a 2 h exposure to 50 ppm CO or a control background from conditioned-air exposure. Upon removal from the nose-only inhalation holder, signs of mild lethargy and decreased activity were evident for 2 min for conditioned-air controls and 50 ppm CO exposure groups and 3-4 min following 4000 ppm CO. Performance on a two-way shuttle box active avoidance task showed no differences between 50 ppm CO rats and conditioned-air controls while the 4000 ppm CO exposed groups showed a significant decrease in avoidance and escape responses. Histological examination showed no evidence of delayed neuronal death or astrocyte reactivity in the hippocampus or cerebellum; however, a distinct focal staining of reactive microglia in both regions was evident in animals exposed to 4000 ppm CO. While 50 ppm CO (5% COHb) alone produced no disruption in avoidance performance, microglia staining in the cerebellum was significantly increased over conditioned-air controls. This regional and focal response of microglia suggests the need for further study regarding such subtle cellular changes and their relationship with COHb levels.

Psychometric properties of the parental stressor scale: infant hospitalization.

PURPOSE: This article reports the development and psychometric properties of the Parental Stressor Scale: Infant Hospitalization (PSS:IH), an instrument designed to measure parents' perceptions of stress associated with having their infant admitted to the hospital. SUBJECTS: Eighty-one mothers and 43 fathers of medically fragile, hospitalized infants.Design and methods Psychometric study of the PSS:IH, an instrument that was adapted from the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) using literature review, parent interviews, and professional experts. Psychometric analysis was conducted from data collected in a longitudinal study of parents of medically fragile infants. Main outcome measure PSS:IH. RESULTS: Correlation coefficients demonstrate its internal consistency reliability. Construct validity is supported by significant correlations between the PSS:IH scores during hospitalization with maternal distress after discharge. CONCLUSIONS: The PSS:IH can be used as an outcome assessment instrument for quality assurance and in clinical research. Additional research could evaluate the scale for use in different populations and settings.

Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid.

BACKGROUND: Prostate specific antigen (PSA) is a well-established marker of prostate cancer, but it can also degrade extracellular matrix proteins such as fibronectin and could be involved in tumor progression and metastasis. In this study, we have addressed the use of boric acid and 3-nitrophenyl boronic acid (NPBA) as PSA inhibitors in vitro. METHODS: The inhibition of PSA by boric acid was studied by using specific fluorogenic substrates. Fibronectin, a biologically relevant substrate for PSA, was used as a substrate in a zymographic assay, and the degradation of fibronectin by PSA in the presence of boric acid and NPBA was followed by Western Blot. RESULTS: Low concentrations of boric acid partially inhibited the proteolytic activity of PSA toward a synthetic fluorogenic substrate. Also, by Western blot, we have found significant inhibition in the proteolysis of fibronectin by PSA in the presence of boric acid as well as NPBA. Results indicate that the boronated compounds used in this study can be used for the modulation of PSA activity. CONCLUSION: PSA activity is inhibited in vitro by boric acid and NPBA. If degradation of fibronectin by PSA were, in fact, an important step in the progression of prostate cancer, then borate-induced inhibition of PSA activity should help reduce the development and proliferation of prostate carcinomas.