title: [The role played by calcium in neuronal injury following neonatal hypoxia or convulsions].
abstract: OBJECTIVE
  Calcium plays a complex and pivotal role both in neuronal development and function, and in hypoxia/ ischemia-induced cell death. In this paper, we review current concepts of calcium function emphasizing the neonatal period.
  
  
  METHODS
  Calcium enters the neuron through glutamate receptors (NMDA and AMPA) located on the neuronal membrane. After hypoxia or seizures, there is a conformational change of the receptors, with increased flow of calcium into the cytoplasm. Cytoplasmatic calcium triggers activation of several free-radical generation pathways, including the nitric oxide pathway, with a deleterious effect upon the neuron. Calcium then enters the neuronal nucleus, through specific receptors on the nuclear membrane. In our experience, hypoxia and neonatal seizures create nuclear membrane dysfunction, increasing the nitric-oxide-dependent flow of calcium into the nucleus. Nuclear calcium increase is critical for genetic transcription, pro-apoptotic gene activation and a cascade of biochemical and molecular events that lead to an increase of caspases and apoptotic neuronal death.
  
  
  CONCLUSIONS
  Calcium has a crucial role in neuronal damage after neonatal hypoxia or seizures. A better knowledge of the pathogenic mechanisms that lead to neuronal damage after neonatal hypoxia or seizures will assist in future development of efficacious neuroprotective therapies.
authors.affiliation: Sección de Neurología, Departamento de Pediatría, St. Christopher's Hospital for Children, Filadelfia, PA 19134, Estados Unidos. ignacio.valencia@drexelmed.edu
authors.forename: I
authors.initials: I
authors.lastname: Valencia
authors.forename: O P
authors.initials: OP
authors.lastname: Mishra
authors.forename: A
authors.initials: A
authors.lastname: Zubrow
authors.forename: K
authors.initials: K
authors.lastname: Fritz
authors.forename: C D
authors.initials: CD
authors.lastname: Katsetos
authors.forename: M
authors.initials: M
authors.lastname: Delivoria-Papadopoulos
authors.forename: A
authors.initials: A
authors.lastname: Legido
mesh_terms: D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D002534:Hypoxia, Brain / Q000150:complications / Q000209:etiology*; D007231:Infant, Newborn; D009474:Neurons / Q000378:metabolism; D012640:Seizures / Q000209:etiology*
chemical_list: D002118:Calcium