title: Apoptotic mitochondrial pathway in neurones and astrocytes after neonatal hypoxia-ischaemia in the rat brain.
abstract: Neuronal apoptosis plays an essential role in early brain development and contributes to secondary neuronal loss after acute ischaemia. Recent studies have provided evidence that caspase-3 is an important downstream event after hypoxia-ischaemia in the immature brain, but a minor event in the adult brain. Our investigations have focused on cell populations that expressed apoptotic effectors in the enzymatic death pathway including cytochrome c, caspase-9 and caspase-3. Expression, activation and cellular localization of these proteins were studied using cleavage of fluorogenic substrate and immunohistochemistry in neonatal rat brain after unilateral focal ischaemia. Caspase-3 enzyme activity was elevated in brain homogenate between 6 and 48 h after reperfusion. This activation was preceded by that of caspase-9, between 3 and 24 h. Apoptotic cell death was finally accomplished by poly-ADP-ribose polymerase cleavage, an endogenous caspase-3 substrate. In addition, immunodetection demonstrated that cytochrome c and activated caspase-9 and caspase-3 were expressed not only in the neurones, the primarily affected cells, but also within the astrocytes, which constituted a dense network delineating the infarct. These results suggested that glial injury may promote the formation of cystic lesions such as those observed clinically in the newborn brain.
authors.affiliation: Université René Descartes, Laboratoire de Pharmacologie, Faculté de Pharmacie, 4 avenue de l'observatoire, 75006 Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Benjelloun
authors.forename: L-M
authors.initials: LM
authors.lastname: Joly
authors.forename: B
authors.initials: B
authors.lastname: Palmier
authors.forename: M
authors.initials: M
authors.lastname: Plotkine
authors.forename: C
authors.initials: C
authors.lastname: Charriaut-Marlangue
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003574:Cytochrome c Group; D011065:Poly(ADP-ribose) Polymerases; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases