Abnormal cerebral neuronal migration in a rat model of intrauterine growthretardation induced by synthetic thromboxane A(2)

Many reports have associated intrauterine growth retardation (IUGR) with ad verse neurological outcome, but the underlying pathology is imperfectly und erstood. We have developed a new rat model of IUGR using maternal administr ation of synthetic thromboxane A, (STA,). In the present study, the effect of this insult on neuronal migration in the rat cerebral cortex was examine d. Bromodeoxyuridine (BrdU), a time-specific cell marker was administered i ntraperitoneally to the mothers on embryonic day (E) 19. At postnatal day ( P) 3, P4, P5, and P6, pups were terminally anesthetized and brains were rem oved. BrdU-labeled cells were detected immunohistochemically and counted in cerebrum, which was divided into the cortical plate (CP), the intermediate zone, and the subventricular/ventricular zone (SVZ + VZ). Numbers of label ed cells in the three areas over time were compared between IUGR and contro l animals. Numbers of labeled cells in SVZ + VZ were significantly greater in IUGR than in controls at P3, 5, and 6 (P < 0.05). In contrast, labeled c ells in the CP were significantly less abundant in IUGR animals than in con trols at P3, 4, and 6 (P < 0.05). We concluded that neuronal migration was delayed in IUGR rats. (C) 2000 Elsevier Science Ireland Ltd. All rights ret urned.