OBJECTIVE: Periventricular leukomalacia is the predominant type of brain injury in preterm infants underlying the development of cerebral palsy. Periventricular leukomalacia has its peak incidence at 23 to 32 weeks postconceptional age characterized by extensive oligodendrocyte migration and maturation. Oxygen toxicity has been identified as a possible contributing factor to the pathogenesis of cerebral palsy in survivors of preterm birth. 17beta-estradiol (E2) is important for the development and function of the central nervous system. Furthermore, neuroprotective properties have been attributed to estrogens. We examined the effect of E2 on hyperoxia-induced cell death in the developing white matter in the rat brain. METHODS: Six-day-old (P6) rat pups, the immature oligodendroglial cell line (OLN-93), and primary oligodendrocyte cultures were subjected to 80% O(2) in the presence or absence of E2 (600 microg/kg intraperitoneally in vivo, 10(-6)-10(-10)M in vitro). Cell counts and lactate dehydrogenase assay were used to assess cell survival. Immunoblot analysis was used for detection of estrogen receptor expression and investigation of apoptotic signaling pathways. White matter injury was assessed by myelin basic protein immunocytochemistry at P11. RESULTS: E2 produced significant dose-dependent protection against oxygen-induced apoptotic cell death in primary oligodendrocytes. Treatment with E2 prevented hyperoxia-induced proapoptotic Fas-upregulation and caspase-3 activation. Finally, E2 antagonized hyperoxia-induced inactivation of extracellular signal-regulated kinase 1 and 2 and Akt, key kinases of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase cell survival promoting pathways, respectively. Loss of myelin basic protein labeling was seen in P11 pups after oxygen exposure, and E2 attenuated this injury. INTERPRETATION: These results suggest a possible role for estrogens in the prevention of neonatal oxygen-induced white matter injury.
OBJECTIVE:Periventricular leukomalacia is the predominant type of brain injury in preterm infants underlying the development of cerebral palsy. Periventricular leukomalacia has its peak incidence at 23 to 32 weeks postconceptional age characterized by extensive oligodendrocyte migration and maturation. Oxygentoxicity has been identified as a possible contributing factor to the pathogenesis of cerebral palsy in survivors of preterm birth. 17beta-estradiol (E2) is important for the development and function of the central nervous system. Furthermore, neuroprotective properties have been attributed to estrogens. We examined the effect of E2 on hyperoxia-induced cell death in the developing white matter in the rat brain. METHODS: Six-day-old (P6) rat pups, the immature oligodendroglial cell line (OLN-93), and primary oligodendrocyte cultures were subjected to 80% O(2) in the presence or absence of E2 (600 microg/kg intraperitoneally in vivo, 10(-6)-10(-10)M in vitro). Cell counts and lactate dehydrogenase assay were used to assess cell survival. Immunoblot analysis was used for detection of estrogen receptor expression and investigation of apoptotic signaling pathways. White matter injury was assessed by myelin basic protein immunocytochemistry at P11. RESULTS:E2 produced significant dose-dependent protection against oxygen-induced apoptotic cell death in primary oligodendrocytes. Treatment with E2 prevented hyperoxia-induced proapoptotic Fas-upregulation and caspase-3 activation. Finally, E2 antagonized hyperoxia-induced inactivation of extracellular signal-regulated kinase 1 and 2 and Akt, key kinases of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase cell survival promoting pathways, respectively. Loss of myelin basic protein labeling was seen in P11 pups after oxygen exposure, and E2 attenuated this injury. INTERPRETATION: These results suggest a possible role for estrogens in the prevention of neonatal oxygen-induced white matter injury.
Authors: Billy Sperlich; Christoph Zinner; Anna Hauser; Hans-Christer Holmberg; Jennifer Wegrzyk Journal: Sports Med Date: 2017-03 Impact factor: 11.136
Authors: Simone Stark; Alexandra Schuller; Marco Sifringer; Bettina Gerstner; Felix Brehmer; Sven Weber; Rodica Altmann; Michael Obladen; Christoph Buhrer; Ursula Felderhoff-Mueser Journal: Neurotox Res Date: 2008 May-Jun Impact factor: 3.911