Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic ventricular dilatation with long-term survival into adulthood.
OBJECTIVE
post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in neonatal care, with sequelae extending beyond childhood. Its management is important in determining outcome. Although rodent hydrocephalus models have been developed, PHVD, as a specific entity with a distinct pathophysiology, has not been studied in a small animal model surviving to adulthood. Our objective is to evaluate survival, to adulthood, in our immature (7-day-old, P7) neonatal rat model, and to analyse early motor reflexes and fine motor and cognitive function, and neuropathology, at 8-12 weeks.


METHODS
sixty-six rats underwent sequential bilateral stereotactic intraventricular haemorrhage (IVH); 36 more acted as controls. Staircase and radial maze evaluations were carried out at 7-11 weeks; animals were sacrificed at 12 weeks. Post mortem ventricular size and corpus callosum thickness were determined.


RESULTS
seventy-six per cent of IVH animals developed PHVD; median (interquartile range) composite ventricular area was 3.46 mm(2) (2.32-5.24). Sixteen (24%) animals demonstrated severe ventricular dilatation (area > 5 mm(2) ). 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. Histopathology confirmed PHVD, ependymal disruption and 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).


CONCLUSIONS
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.
Aquilina
K
K
School of Clinical Sciences, University of Bristol Department of Neurosurgery, Frenchay Hospital, Bristol, UK.
Chakkarapani
E
E
Love
S
S
Thoresen
M
M
D000818:Animals; D000831:Animals, Newborn; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D004108:Dilatation, Pathologic / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007858:Learning / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar