Characterization of acute brain injuries and neurobehavioral profiles in a rabbit model of germinal matrix hemorrhage.
OBJECTIVE
Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is the most common neurological problem of premature infants and has enormous financial and social impact. Despite this, there is no standardized animal model of IVH depicting acute brain injuries.


METHODS
We delivered rabbit-pups prematurely at 29-day gestation by C-section, administered intraperitoneal glycerol to the pups at 3-hour postnatal age to induce IVH, and evaluated the brain for evidence of injuries.


RESULTS
About 80% of glycerol-treated pups developed gross IVH. We found greater neutrophil and microglia infiltration around the ventricles (periventricular zone) in pups with IVH than in controls. We noted more apoptosis and neuronal degeneration in the periventricular zone than in the neocortex in pups with IVH, but not in controls. There was evidence of axonal damage revealed by beta-amyloid precursor protein and neurofilament immunolabeling. Neurobehavioral testing showed that pups with IVH were more wobbly with lesser capability to walk on inclination than pups without IVH. There was no evidence of acute systemic toxicity in the glycerol-treated pups. An evaluation of autopsy materials from premature infants revealed similar evidence of apoptosis and cellular infiltration in the periventricular zone in cases with IVH, but not in cases without IVH-suggesting clinical relevance of the model.


CONCLUSIONS
The study provides an instructive animal model of IVH with evidence of acute brain injuries that can be used to evaluate strategies in prevention of IVH and acute posthemorrhagic complications.
Georgiadis
Paraskevi
P
Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, USA. Pballabh@msn.com
Xu
Hongmin
H
Chua
Caroline
C
Hu
Furong
F
Collins
Lee
L
Huynh
Chau
C
Lagamma
Edmund F
EF
Ballabh
Praveen
P
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology / Q000523:psychology; D002552:Cerebral Ventricles / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D005990:Glycerol / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000473:pathology; D007274:Injections, Intraperitoneal; D017628:Microglia / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000209:etiology; D009504:Neutrophils / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth; D011817:Rabbits; D016037:Single-Blind Method; D014463:Ultrasonography
D005990:Glycerol