Astrocytic demise in the developing rat and human brain after hypoxic-ischemic damage.
In order to approach the physiopathological mechanism underlying the selective susceptibility of the immature brain to hypoxia-ischemia (HI), we have compared the lesions experimentally induced in postnatal day 7 rats using a model of neonatal stroke with those occurring in human fetal and neonatal brains. We first observed that gray and white matter lesions demonstrated a similar organization (core with cell loss and/or cavity and penumbra) and evolutionary pattern between experimental and human HI lesions. We then observed that, in the intermediate white matter, GFAP- and vimentin-positive astrocytes exhibited clasmatodendrosis and represent a major cell population involved in cell death in human brains (56.3 and 67.9%, respectively). In rat brains, GFAP- and TUNEL-positive astrocytes were also highly vulnerable, increasing between 6 (31%) and 72 (58%) hours after ischemia. Together, these results indicate that astroglial dysfunction may play a critical role in determining the progress and outcome of acute hypoxic-ischemic injury particularly in the developing brain.
Gelot
Antoinette
A
Département de Neuropathologie, Service d'Anatomie et Cytologie Pathologiques, Hôpital A. Trousseau, Paris, France.
Villapol
S
S
Billette de Villemeur
Thierry
T
Renolleau
Sylvain
S
Charriaut-Marlangue
Christiane
C
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D005260:Female; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D013194:Staining and Labeling; D014746:Vimentin / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin