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Updated: Jul 5, 2026
Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection of Hemoglobin
Published on: August 25, 2022
A neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation
Kristian Aquilina1, Catherine Hobbs, Shobha Cherian
1Department of Child Health, University of Bristol, Clinical Sciences at South Bristol, United Kingdom.
Insights
A new piglet model accurately mimics neonatal intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD). This model allows for close monitoring and evaluation of potential treatments for these common, disabling conditions in premature infants.
Area of Science:
- Neonatal physiology
- Neurology
- Animal modeling
Background:
- Intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD) are significant causes of disability in premature infants.
- Current management of neonatal IVH lacks consensus, with cerebrospinal fluid (CSF) shunts having high complication rates.
- Understanding the pathophysiology of IVH/PHVD and monitoring treatment effects requires suitable models.
Purpose of the Study:
- To develop and validate a neonatal large animal model of IVH with long-term survival.
- To enable close physiological and ultrasonographic monitoring of IVH and PHVD development.
- To provide a platform for evaluating novel management strategies for IVH and PHVD.
Main Methods:
- Fourteen neonatal piglets (3-24 hours old) were used.
- Animals received injections of autologous blood, blood with elevated hematocrit, or artificial CSF; controls received no injection.
- Intracranial pressure, electroencephalography, and serial cranial ultrasonography were monitored; histological evaluation was performed.
Main Results:
- Progressive ventricular dilation was observed in piglets injected with blood.
- Elevated hematocrit blood injections resulted in the greatest ventricular dilation.
- Histological analysis revealed subarachnoid fibrosis in hydrocephalic piglets.
Conclusions:
- The developed piglet model accurately replicates human neonatal IVH and PHVD.
- The model allows for prolonged survival and detailed monitoring of physiological and ultrasonographic parameters.
- This model is suitable for evaluating both noninvasive and surgical interventions for IVH and PHVD.
Object:
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.
