Pharmacological Neuroprotection after Perinatal Hypoxic-Ischemic Brain Injury

Xiyong      Fan; Annemieke      Kavelaars; Cobi      J. Heijnen; Floris      Groenendaal; Frank      van Bel

Abstract

Perinatal hypoxia-ischemia (HI) is an important cause of neonatal brain injury. Recent progress in the search for neuroprotective compounds has provided us with several promising drugs to reduce perinatal HI-induced brain injury. In the early stage (first 6 hours after birth) therapies are concentrated on prevention of the production of reactive oxygen species or free radicals (xanthine-oxidase-, nitric oxide synthase-, and prostaglandin inhibition), anti-inflammatory effects (erythropoietin, melatonin, Xenon) and anti-apoptotic interventions (nuclear factor kappa B- and c-jun N-terminal kinase inhibition); in a later stage stimulation of neurotrophic properties in the neonatal brain (erythropoietin, growth factors) can be targeted to promote neuronal and oligodendrocyte regeneration. Combination of pharmacological means of treatment with moderate hypothermia, which is accepted now as a meaningful therapy, is probably the next step in clinical treatment to fight post-asphyxial brain damage. Further studies should be directed at a more rational use of therapies by determining the optimal time and dose to inhibit the different potentially destructive molecular pathways or to enhance endogenous repair while at the same time avoiding adverse effects of the drugs used.

Keywords: Brain, hypoxia, ischemia, neonate, neuroprotection, pharmacology, neonatal brain injury, nitric oxide synthase, prostaglandin inhibition, xanthine-oxidase, erythropoietin, melatonin, Xenon, anti-apoptotic, reoxygenation, hypothermia, neurotransmitters, glutamate, N-methyl-D-aspartate, free radi-cals, hydrogen peroxide, neutrophils, macrophages, microglia, N-terminal kinase, Growth Factors, peroxynitrite, free radicals, neurogenesis, anti-oxidative, anti-inflammatory, asphyxia, nicardipine, Calcium blockers, flunarizine, hydroxyl radicals, prostaglandin, Allopurinol, chelate, oxypurinol, asphyxiated, pro-free radical, ameliorate, 7-nitroindazole, aminoguanidine, erythroid progenitor, astrocytes, microglial cells, umbilical, etanercept, TNF-receptor, Domain, intraperitoneally, caspase-3, Hyperbaric Oxygen, sensorimotor, Post-HI Period, Trophic Factor, subventricular, oligodendrocytes, angiogenesis