A neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation.
OBJECTIVE
The combination of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD) remains an important cause of disability in children surviving prematurity. Currently, there is no clear agreement on the management of neonatal IVH, apart from the eventual insertion of a shunt to control PHVD. Cerebrospinal fluid (CSF) shunts are associated with a relatively high complication rate in this population. The development of new treatment options requires greater understanding of the pathophysiological mechanisms of IVH and PHVD, as well as an opportunity to monitor closely their effects on the immature brain. The authors have developed a neonatal large animal model of IVH with long-term survival, allowing the full development of PHVD.


METHODS
Fourteen piglets that were 3 to 24 hours old were randomized to receive slow injections of autologous blood, autologous blood with elevated hematocrit, or artificial CSF after induction of general anesthesia. A fourth group served as controls. All animals underwent surgery to form an artificial fontanelle at the bregma. Physiological parameters, including intracranial pressure and electroencephalography, were monitored during injection.


RESULTS
Serial cranial ultrasonography studies performed during the 23- to 44-day survival period demonstrated progressive ventricular dilation in the animals injected with blood. Ventricular volumes, measured with image analysis software, confirmed the highest dilation after injection of blood with an elevated hematocrit. Histological evaluation showed fibrosis in the basal subarachnoid space of hydrocephalic piglets.


CONCLUSIONS
This piglet model closely replicates human neonatal IVH and PHVD. It allows detailed physiological and ultrasonographic monitoring over a prolonged survival period. It is suitable for evaluation of noninvasive as well as surgical options in the management of IVH and PHVD.
Aquilina
Kristian
K
Department of Child Health, University of Bristol, Clinical Sciences at South Bristol, United Kingdom.
Hobbs
Catherine
C
Cherian
Shobha
S
Tucker
Alexander
A
Porter
Helen
H
Whitelaw
Andrew
A
Thoresen
Marianne
M
D000818:Animals; D000831:Animals, Newborn; D001769:Blood; D002552:Cerebral Ventricles / Q000473:pathology*; D002555:Cerebrospinal Fluid; D004108:Dilatation, Pathologic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006400:Hematocrit; D007276:Injections, Intraventricular; D020300:Intracranial Hemorrhages / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D007427:Intracranial Pressure; D010865:Pilot Projects; D013552:Swine