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

Protective Effect of Hydroalcoholic Root Extract of Rubia cordifolia in Indomethacin-Induced Enterocolitis in Rats

This study was undertaken to investigate the possible effect of hydroalcoholic root extract of Rubia cordifolia against indomethacin-induced enterocolitis in rats. Male Wistar rats received vehicle or hydroalcoholic root extract of Rubia cordifolia (300 and 600 mg/kg) for 11 consecutive days. Enterocolitis was induced by subcutaneous administration of indomethacin (7.5 mg/kg) on 8th and 9th day. The colonic mucosal injury was assessed by macroscopic scoring and histopathological examination. Furthermore, the serum lactate dehydrogenase activity was estimated. Indomethacin treatment to rats produced acute intestinal inflammation, manifested by a thickening of the bowel wall, mesenteric haemorrhage, mesentery adhesion and multiple mucosal ulcers of small intestine and colon. Treatment with hydroalcoholic root extract of Rubia cordifolia revealed less damage to intestinal tissue and decreased serum lactate dehydrogenase activity which was elevated by induction of colitis. The present data suggests protective effect of Rubia cordifolia in indomethacin-induced enterocolitis and may be beneficial in patients with inflammatory bowel diseases