Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins

Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD+ tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase β, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care

Social tie, social capital, and social behavior: Toward an integrative model of informal exchange

What is the unique nature of social capital that differentiates itself from other forms of capital? How should we conceptualize and operationalize social capital? What are the major drivers and outcomes of social capital? To address the three questions, I apply the duality lens—the perspective of regarding each entity as a paradox consisting of two contrasting yet interdependent components—to social capital for an integrative model of informal exchange. The focus of this paper is on the duality relationship between the content variables (social tie, social capital, social behavior along two basic dimensions: trust for tie strength and option for network structure) and the process variables (antecedent, content, process, and consequence) toward a geocentric framework of formal–informal exchange. I intend to make two contributions. First, the conceptualization and operationalization of social capital is developed from the duality lens of formal–informal exchange so as to identify the unique nature of social capital as an informal entity. Second, a holistic, dynamic, and dialectic model of social capital is provided to explore the causal links between various elements related to social capital. Copyright Springer Science+Business Media, LLC 2007Social capital, Trust, Option, Tie strength, Network structure, Informal exchange,