Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury.

Despite the prevalence of preterm brain injury, there are no established neuroprotective strategies to prevent or alleviate mild-to-moderate inflammation-related brain injury. Perinatal infection and inflammation have been shown to trigger acute neuroinflammation, including proinflammatory cytokine release and gliosis, which are associated with acute and chronic disturbances in brain cell survival and maturation. These findings suggest the hypothesis that the inhibition of peripheral immune responses following infection or nonspecific inflammation may be a therapeutic strategy to reduce the associated brain injury and neurobehavioral deficits.

Long-term coordinated microstructural disruptions of the developing neocortex and subcortical white matter after early postnatal systemic inflammation.

Severe postnatal systemic infection is highly associated with persistent disturbances in brain development and neurobehavioral outcomes in survivors of preterm birth. However, the contribution of less severe but prolonged postnatal infection and inflammation to such disturbances is unclear. Further, the ability of modern imaging techniques to detect the underlying changes in cellular microstructure of the brain in these infants remains to be validated.

Role of Hemichannels in CNS Inflammation and the Inflammasome Pathway.

Neurodegenerative, cardiovascular, and metabolic disorders, once triggered, share a number of common features, including sustained inflammatory cell activation and vascular disruption. These shared pathways are induced independently of any genetic predisposition to the disease or the precise external stimulus. Glial cells respond to injury with an innate immune response that includes release of proinflammatory cytokines and chemokines.

A Critical Review of Models of Perinatal Infection.

One of the central, unanswered questions in perinatology is why preterm infants continue to have such poor long-term neurodevelopmental, cognitive and learning outcomes, even though severe brain injury is now rare. There is now strong clinical evidence that one factor underlying disability may be infection, as well as nonspecific inflammation, during fetal and early postnatal life. In this review, we examine the experimental evidence linking both acute and chronic infection/inflammation with perinatal brain injury and consider key experimental determinants, including the microglia response, relative brain and immune maturity and the pattern of exposure to infection.

Analgesics, sedatives, anticonvulsant drugs, and the cooled brain.

Multiple randomized controlled trials have shown that prolonged, moderate cerebral hypothermia initiated within a few hours after severe hypoxia-ischemia and continued until resolution of the acute phase of delayed cell death reduces mortality and improves neurodevelopmental outcome in term infants. The challenge is now to find ways to further improve outcomes. In the present review, we critically examine the evidence that conventional analgesic, sedative, or anticonvulsant agents might improve outcomes, in relation to the known window of opportunity for effective protection with hypothermia.

Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency.

In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age.