Expression of ephrinB2 and EphB4 in a neonatal rat model of periventricular white matter damage

Background: Periventricular white matter damage (PWMD), also termed periventricular leukomalacia, is the predominant neurologic lesion in preterm infants. It appears to relate in part to the development of the vascular supply to the cerebral white matter. We investigated whether, in case of severe hypoxia-ischemia, the vascular system would be subject to severe damage or remodeled. Aims: To evaluate microvessel density (MVD) and the use of ephrinB2 and its receptor EphB4 to mark arterioles and venules to establish the correct anatomic assignment of the remodeled vessels in a hypoxia-induced PWMD rat model. Methods: Postnatal day 3 rats underwent permanent ligation of the right common carotid artery followed by 6% O-2 for 4 h (hypoxia-ischemia) or sham operation and normoxic exposure (sham). MVD and levels of ephrinB2 and EphB4, which are respectively regarded as relatively specific molecular markers of arteries and veins, were determined at postnatal day 7. Results: Compared with sham rats, MVD, ephrinB2 and EphB4 levels were higher in the brains of hypoxic-ischemic rats. Similar percentages of vessels expressed ephrinB2 and EphB4 in sham rats, but expression of ephrinB2 was greater in brains injured by hypoxia-ischemia. Conclusions: Following hypoxic-ischemic injury to the rat brain, microvessels were remodeled and more arterioles than venules were acquired.