Consequences of intraventricular hemorrhage in a rabbit pup model.
OBJECTIVE
Intraventricular hemorrhage (IVH) is a common complication of prematurity that results in neurological sequelae, including cerebral palsy, posthemorrhagic hydrocephalus, and cognitive deficits. Despite this, there is no standardized animal model exhibiting neurological consequences of IVH in prematurely delivered animals. We asked whether induction of moderate-to-severe IVH in premature rabbit pups would produce long-term sequelae of cerebral palsy, posthemorrhagic hydrocephalus, reduced myelination, and gliosis.


METHODS
The premature rabbit pups, delivered by cesarean section, were treated with intraperitoneal glycerol at 2 hours postnatal age to induce IVH. The development of IVH was diagnosed by head ultrasound at 24 hours of age. Neurobehavioral, histological, and ultrastructural evaluation and diffusion tensor imaging studies were performed at 2 weeks of age.


RESULTS
Although 25% of pups with IVH (IVH pups) developed motor impairment with hypertonia and 42% developed posthemorrhagic ventriculomegaly, pups without IVH (non-IVH) were unremarkable. Immunolabeling revealed reduced myelination in the white matter of IVH pups compared with saline- and glycerol-treated non-IVH controls. Reduced myelination was confirmed by Western blot analysis. There was evidence of gliosis in IVH pups. Ultrastructural studies in IVH pups showed that myelinated and unmyelinated fibers were relatively preserved except for focal axonal injury. Diffusion tensor imaging showed reduction in fractional anisotropy and white matter volume confirming white matter injury in IVH pups.


CONCLUSIONS
The rabbit pups with IVH displayed posthemorrhagic ventriculomegaly, gliosis, reduced myelination, and motor deficits, like humans. The study highlights an instructive animal model of the neurological consequences of IVH, which can be used to evaluate strategies in the prevention and treatment of posthemorrhagic complications.
Chua
Caroline O
CO
Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY 10595, USA.
Chahboune
Halima
H
Braun
Alex
A
Dummula
Krishna
K
Chua
Charles Edrick
CE
Yu
Jen
J
Ungvari
Zoltan
Z
Sherbany
Ariel A
AA
Hyder
Fahmeed
F
Ballabh
Praveen
P
D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D020833:Diffuse Axonal Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D005990:Glycerol / Q000633:toxicity; D006984:Hypertrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020547:Lateral Ventricles / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D046529:Microscopy, Electron, Transmission; D009069:Movement Disorders / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D047928:Premature Birth / Q000473:pathology / Q000503:physiopathology*; D011817:Rabbits; D014463:Ultrasonography
D005990:Glycerol