Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic ventricular dilatation with long-term survival into adulthood

Aims. Post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in neonatal care, with sequelae extending beyond childhood. Management of PHVD is an important determinant of outcome. Although small animal hydrocephalus models have been developed, PHVD, as a specific entity with a distinct pathophysiology, has not yet been studied in a rodent model surviving to adulthood. The objective of this study is to evaluate long-term survival, to adulthood, in our immature (7 day old, P7) neonatal rat model, and to analyse early motor reflexes as well as fine motor and cognitive function, and neuropathology, at 8 to 10 weeks. Methods. Sixty-six rats underwent sequential bilateral stereotactic IVH; a further 36 acted as controls. Staircase and radial maze evaluations were carried out at 7 – 11 weeks; they were sacrificed at 12 weeks. Brains were perfused and fixed in formalin; ventricular size and corpus callosum thickness were determined. Results. 76% of IVH animals developed PHVD, with a median (IQR) composite ventricular area of 3.46 mm2 (2.32 – 5.24). Sixteen (24%) animals demonstrated severe ventricular dilatation (area > 5 mm2). IVH animals failed to improve on the negative geotaxis test at 2 weeks. The staircase test did not identify any significant difference. On the radial maze animals with severe PHVD made more reference errors than those with moderate or no ventricular dilatation. Histopathology confirmed PHVD, ependymal disruption and extensive periventricular white matter injury. Median anterior corpus callosum thickness was significantly lower in IVH animals (0.35 mm) than in those not undergoing IVH (0.43 mm). Conclusion. Our P7 neonatal rat IVH model is suitable for long-term survival and replicates many of the morphological and some of the behavioural features seen in human PHVD.