CONICET | Buscador de Institutos y Recursos Humanos

Hypoxic/ischemic damage is one of the main causes of Periventricular Leukomalacia, an injury of periventricular white matter connected with neurological dysfunction in premature infants. Studies in rodents have focused on the physiopathology of neuronal damage while injury on the white matter has received much less consideration, although it is the principal contributor to the neurological dysfunction. The most widely used model of neonatal hypoxia involves permanent carotid artery ligation in P7 rats and their later submission to 2.25 h of hypoxia. This model is difficult to use in mice and, consequently, in transgenic animals due to their anatomical features. Recently, a hypoxic neonatal model has been described, which uses P1 rats exposed to 8% O2 during 2 h. As we have C57BL-6 transgenic mice expressing EGFP upon the promoter of CNPase, a characteristic oligodendroglial marker, we decided to evaluate proliferation, activation, differentiation and apoptosis of glial cells and their precursors in rats and CNPase-EGFP mice submitted to 2 h of hypoxia and studied at P1, P4, P14 and P21. Our results show myelination damage evaluated by immunohistochemistry of MBP and CNPase expression in the cingulum. This hypomyelination was accompanied by astroglial activation evidenced by an increase in GFAP immunostaining in the cingulum and striatum, particularly in the perivascular area. An increase in the number of GFAP+ cells was also observed in the subventricular zone (SVZ), indicating a rise in the number of neural stem cells. Moreover, an increase in proliferation evaluated by BrdU incorporation was observed in these animals, especially in the corpus callosum, cingulum and SVZ. Results suggest that this might be a good model to study the mechanisms involved in oligodendroglial damage in neonatal hypoxia.