Perinatal neuroprotection

Abstract

Fetal or neonatal brain injury can result in lifelong neurologic disability. The most significant risk factor for perinatal brain injury is prematurity; however, in absolute numbers, full-term infants represent the majority of affected children. Research on strategies to prevent or mitigate the impact of perinatal brain injury (“perinatal neuroprotection”) has established the mitigating roles of magnesium sulfate administration for preterm infants and therapeutic hypothermia for term infants with suspected perinatal brain injury. Banked umbilical cord blood, erythropoietin, and a number of other agents that may improve neuronal repair show promise for improving outcomes following perinatal brain injury in animal models. Other preventative strategies include delayed umbilical cord clamping in preterm infants and progesterone in women with prior preterm birth or short cervix and avoidance of infections. Despite these advances, we have not successfully decreased the rate of preterm birth, nor are we able to predict term infants at risk of hypoxic brain injury in order to intervene prior to the hypoxic event. Further, we lack the ability to modulate the sequelae of neuronal cell insults or the ability to repair brain injury after it has been sustained. As a consequence, despite exciting advances in the field of perinatal neuroprotection, perinatal brain injury still impacts thousands of newborns each year with significant long-term morbidity and mortality.

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

“…47,51,52 Although therapeutic hypothermia has improved the outlook of infants with HIE, 53,54 there remains a pressing need for neuroprotective therapies that will further reduce the high rate of neurologic disabilities. [55][56][57] We reported the safety and pharmacokinetics of high-dose Epo when given together with hypothermia. 16,17 Darbepoetin, a long-acting formulation of Epo, has also been shown to be safe in newborns undergoing hypothermia for HIE.…”

Inflammatory Bowel Disease: How Effective Is TNF-α Suppression?

“…Increased tissue concentration of TNF-α in IBD patients can lead undifferentiated M0 macrophages to polarize to M1 macrophages, classically activated macrophages [20]. M1 macrophages can also be derived from M2 in the presence of high levels of IFN-γ, a proinflammatory cytokine [21]. In contrast, M2 (alternatively activated macrophages) are induced by anti-inflammatory cytokines such as IL-10 and TGF-β [21].…”

“…M1 macrophages can also be derived from M2 in the presence of high levels of IFN-γ, a proinflammatory cytokine [21]. In contrast, M2 (alternatively activated macrophages) are induced by anti-inflammatory cytokines such as IL-10 and TGF-β [21]. The following factors were considered when obtaining a differential equation for M1 macrophage phenotype formation: concentration of tissue factors ( f 1 ) that contribute to macrophage polarization; tissue concentrations of TNF-α ( I α ) , IFN-γ ( I γ ) and TGF-β ( I β ); cytokine specific rates of macrophage activation ( σ Mα , σ Mβ , σ Mγ ) and transition between M1 and M2 phenotypes ( σ Mβ , σ Mγ ), and macrophage apoptosis (decay) rate ( μ M ).…”

Preterm birth and the role of neuroprotection

“…In 2013, the lifetime cost for a child born with cerebral palsy was estimated at $1.1m in the US. 7 In addition, a study that assessed the impact of preterm birth on families found that in the first year 11% had financial difficulties, 26% observed a decrease in social activities, and 28% reported that having a preterm child was emotionally challenging or difficult to accept. 8 Clearly, the prevention of preterm birth and its sequelae would have a substantial impact on both society and individuals.…”