A Novel Preclinical Model of Germinal Matrix Hemorrhage Using Neonatal Rats

Abstract

Background: Germinal matrix hemorrhage (GMH) is a neurological disorder associated with very low birth weight premature infants. This event can lead to post-hemorrhagic hydrocephalus, cerebral palsy, and mental retardation. This study developed a novel animal model for pre-clinical investigations. Methods: Neonatal rats underwent infusion of clostridial collagenase into the right germinal matrix (anterior caudate) region using stereotaxic techniques. Developmental milestones were evaluated over 10 days, cognitive function at 3 weeks, and sensorimotor function at 4 weeks after collagenase infusion. This was accomplished by anthropometric quantifications of cranial, cerebral, cardiac, and splenic growths. Results: Collagenase infusion led to delays in neonatal developmental milestones, followed by cognitive and sensorimotor dysfunctions in the juvenile animals. Cranial growth was accelerated during the first week after injury, and this was followed by significant brain atrophy, splenomegaly, and cardiac hypertrophy 3 weeks later. Conclusion: This study characterized the developmental delays, mental retardation, and cerebral palsy features resembling the long-term clinical course after germinal matrix hemorrhage in premature infants. Pre-clinical testing of therapeutics in this experimental model could lead to improved patient outcomes while expanding upon the pathophysiological understanding of this disease.