[Cell death in neonatal hypoxia-ischemia].
OBJECTIVE
To review the mechanisms of cell death (CD) in the developing brain after hypoxia-ischemia (HI).


METHODS
The possibility of limiting the CD which occurs in serious situations of cerebral HI is based on advances in the understanding of the underlying cellular and molecular mechanisms. Various experimental models offer the opportunity to study these mechanisms in reproducible situations. Relevant concepts are the focal HI as compared to global HI, with well-differentiated patterns of selective vulnerability which depend on vascular and neurochemical factors. In situations of infarct, the distinction between core and penumbra permits the identification of areas of brain tissue which potentially may recover, where the CD occurs, at least partially, more slowly and by apoptosis. Most of this CD occurs during the phase of reperfusion, when the reintroduction of oxygen activates the neurotoxic cascades. Amongst the molecules involved in the early marking of cell damage are the genes c-fos and c-jun, HSP, MAP-2, cytokines, GLUT3 and calpaines. Some of the recent attempts of block post-HI MC are treatments with trophic factors, glucocorticoids and hypothermia.


CONCLUSIONS
Analysis of the time-course of MC in perinatal HI suggest the presence of a therapeutic window. The development of treatments for nerve rescue comes up against the complexity of the mechanisms involved in MC and their potential toxicity in immature brain.
Macaya
A
A
Sección de Neurología Infantil, Hospital Materno-Infantil Vall d'Hebron, Barcelona, España. macaya@cs.vhebron.es
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology* / Q000628:therapy; D007231:Infant, Newborn; D019194:Ischemic Preconditioning; D009336:Necrosis; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology
D018696:Neuroprotective Agents