Abstract
Background and Purpose-: 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. Conclusion-: 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3369-3377 |
| Number of pages | 9 |
| Journal | Stroke |
| Volume | 40 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2009 |
| Externally published | Yes |
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Keywords
- Germinal matrix hemorrhageintraventricular hemorrhage
- Gliosis
- Myelin
- Neurobehavioral testing
- Ventriculomegaly
- White matter
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Clinical Neurology
- Advanced and Specialized Nursing
Cite this
Consequences of intraventricular hemorrhage in a rabbit pup model. / Chua, Caroline O.; Chahboune, Halima; Braun, Alex; Dummula, Krishna; Chua, Charles Edrick; Yu, Jen; Ungvari, Zoltan; Sherbany, Ariel A.; Hyder, Fahmeed; Ballabh, Praveen.
In: Stroke, Vol. 40, No. 10, 10.2009, p. 3369-3377.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Consequences of intraventricular hemorrhage in a rabbit pup model
AU - Chua, Caroline O.
AU - Chahboune, Halima
AU - Braun, Alex
AU - Dummula, Krishna
AU - Chua, Charles Edrick
AU - Yu, Jen
AU - Ungvari, Zoltan
AU - Sherbany, Ariel A.
AU - Hyder, Fahmeed
AU - Ballabh, Praveen
PY - 2009/10
Y1 - 2009/10
N2 - Background and Purpose-: 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. Conclusion-: 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.
AB - Background and Purpose-: 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. Conclusion-: 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.
KW - Germinal matrix hemorrhageintraventricular hemorrhage
KW - Gliosis
KW - Myelin
KW - Neurobehavioral testing
KW - Ventriculomegaly
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=70349682406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349682406&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.109.549212
DO - 10.1161/STROKEAHA.109.549212
M3 - Article
VL - 40
SP - 3369
EP - 3377
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 10
ER -