Presented at the Neonatal Society 2003 Spring Meeting.
Cherian S1, Love S2, Silver I3, Eagle R3, Whitelaw A1, Thoresen M1
1 Division of Child Health, St Michaels Hospital, Bristol BS8 8EG, UK
2 Neuropathology, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK
3 Anatomy, School of Veterinary Sciences, University of Bristol, UK
Introduction: Intraventricular haemorrhage (IVH) continues to be an important predictor of neurological outcome in premature infants. Over half of infants with severe IVH develop progressive ventricular dilatation and up to 40% suffer major neurological sequelae, with prominent motor dysfunction.
Aim: We set out to develop a test battery for motor performance that correlated with pathology in a recently developed model of post-haemorrhagic ventricular dilatation in the neonatal rat (1). This model relies on ventricular distension for the development of post-hemorrhagic ventricular dilatation.
Methods: 80μl injections of citrated rat blood or the same volume of artificial CSF was injected into alternate lateral ventricles of 30 Wistar rat pups on postnatal days 7 and 8. (P7 & 8) 37 uninjected pups served as controls. All were subjected to a battery of 6 neurological tests on P10, 14, 18 and 21. The tests were of righting and postural reflexes, negative geotaxis, grip traction, cliff aversion, and movement across a wire mesh grid. On P21 the rats were perfusion-fixed and blocks of brain processed for histology and ventricular morphometry.
Results: Animals with ventricular dilatation, as a group, had significantly lower motor performance. There was a significant difference between controls and injected animals in grip traction at P14, 18 and 21, negative geotaxis at P14 and movement across a grid at P21. Rat pups injected with blood or CSF who did not develop ventricular dilatation also scored lower than controls on these tests. There was no impairment of cliff aversion or righting reflexes, and postural reflexes remained normal and symmetrical. 77% of rats injected with blood and 40% injected with artificial CSF developed ventricular dilatation with patchy ependymal loss, marked astrocytic gliosis and rarefaction of periventricular white matter. There were no significant differences in the body weights in different groups.
Conclusions: Impaired motor performance is demonstrable as early as 1-2 weeks after the injection of blood or artificial CSF into the ventricles of neonatal rat pups. This is usually associated with hydrocephalus, but some motor dysfunction occurs even in pups that do not become hydrocephalic. Neurological testing in this model should prove useful in assessing the potential of different therapeutic measures after ventricular haemorrhage.
References:
1. Cherian S, Love S, Silver I, Porter H, Whitelaw A, Thoresen M. Post-haemorrhagic ventricular dilatation in the neonate: development and characterisation of a rat model. J Exp Neurology and Neuropathol. (In Press)