transparent gif


Ej inloggad.

Göteborgs universitets publikationer

Delayed cortical impairment following lipopolysaccharide exposure in preterm fetal sheep.

Författare och institution:
Justin M Dean (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Yohan van de Looij (-); Stephane V Sizonenko (-); Gregory A Lodygensky (-); Francois Lazeyras (-); Hayde Bolouri (Institutionen för neurovetenskap och fysiologi); Ingemar Kjellmer (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för pediatrik); Petra S Huppi (-); Henrik Hagberg (Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för obstetrik och gynekologi); Carina Mallard (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
Annals of neurology, 70 ( 5 ) s. 846–856
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
OBJECTIVE: Preterm infants exhibit chronic deficits in white matter (WM) and cortical maturation. Although fetal infection/inflammation may contribute to WM pathology, the factors contributing to cortical changes are largely unknown. We examined the effect of fetal lipopolysaccharide (LPS) exposure on WM and cortical development as assessed by magnetic resonance imaging (MRI), electroencephalography (EEG), and histopathology in fetal sheep at preterm human equivalent age. METHODS: LPS was administered to fetal sheep at 102.5 ± 0.5 days of gestation. Continuous biophysical recordings were analyzed for 10 days after LPS. At postmortem, measurement of cerebral WM and cortical tissue volumes was achieved by stereological techniques. Specific effects of LPS on MRI-assessed T(1) -weighted and T(2) -weighted images, and immunohistochemical expression of oligodendrocytes, proliferating cells, cortical NeuN-positive and Nurr1-positive neurons (subplate marker), and cell death mechanisms were examined. RESULTS: We observed reductions in WM (∼21%; LPS, 1.19 ± 0.04 vs control, 1.51 ± 0.07cm(3) ; p < 0.001) and cortical (∼18%; LPS, 2.34 ± 0.10 vs control, 2.85 ± 0.07cm(3) ; p < 0.001) volumes, associated with overt and diffuse WM injury, T(1) -/T(2) -weighted signal alterations, and reduced numbers of WM oligodendrocytes (LPS, 485 ± 31 vs control, 699 ± 69 cells/mm(2) ; p = 0.0189) and NeuN-positive (LPS, 421 ± 71 vs control 718 ± 92 cells/mm(2) ; p = 0.04) and Nurr1-positive (control, 2.5 ± 0.6 vs LPS, 0.6 ± 0.1 cells/mm(2) ; p = 0.007) cortical neurons after LPS. Moreover, there was loss of the normal maturational increase in cortical EEG amplitude, which correlated with reduced cortical volumes. INTERPRETATION: Fetal exposure to LPS prior to myelination onset can impair both white matter and cortical development in a preclinical large animal model, supporting a role for maternal/fetal infection in the pathogenesis of preterm brain injury. ANN NEUROL 2011.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Reproduktionsmedicin och gynekologi ->
Obstetrik och kvinnosjukdomar ->
Reproduktiv och perinatal omvårdnad
Postens nummer:
Posten skapad:
2011-10-20 10:10
Posten ändrad:
2012-08-16 16:01

Visa i Endnote-format

Göteborgs universitet • Tel. 031-786 0000
© Göteborgs universitet 2007