Consequences of intraventricular hemorrhage in a rabbit pup model

Caroline O. Chua, Halima Chahboune, Alex Braun, Krishna Dummula, Charles Edrick Chua, Jen Yu, Zoltan Ungvari, Ariel A. Sherbany, Fahmeed Hyder, Praveen Ballabh

Research output: Contribution to journalArticle

68 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)3369-3377
Number of pages9
JournalStroke
Volume40
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

Fingerprint

Hemorrhage
Rabbits
Gliosis
Diffusion Tensor Imaging
Cerebral Palsy
Hydrocephalus
Glycerol
Animal Models
Anisotropy
Wounds and Injuries
Cesarean Section
Western Blotting
Head

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

Chua, C. O., Chahboune, H., Braun, A., Dummula, K., Chua, C. E., Yu, J., ... Ballabh, P. (2009). Consequences of intraventricular hemorrhage in a rabbit pup model. Stroke, 40(10), 3369-3377. https://doi.org/10.1161/STROKEAHA.109.549212

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 journalArticle

Chua, CO, Chahboune, H, Braun, A, Dummula, K, Chua, CE, Yu, J, Ungvari, Z, Sherbany, AA, Hyder, F & Ballabh, P 2009, 'Consequences of intraventricular hemorrhage in a rabbit pup model', Stroke, vol. 40, no. 10, pp. 3369-3377. https://doi.org/10.1161/STROKEAHA.109.549212
Chua CO, Chahboune H, Braun A, Dummula K, Chua CE, Yu J et al. Consequences of intraventricular hemorrhage in a rabbit pup model. Stroke. 2009 Oct;40(10):3369-3377. https://doi.org/10.1161/STROKEAHA.109.549212
Chua, Caroline O. ; Chahboune, Halima ; Braun, Alex ; Dummula, Krishna ; Chua, Charles Edrick ; Yu, Jen ; Ungvari, Zoltan ; Sherbany, Ariel A. ; Hyder, Fahmeed ; Ballabh, Praveen. / Consequences of intraventricular hemorrhage in a rabbit pup model. In: Stroke. 2009 ; Vol. 40, No. 10. pp. 3369-3377.
@article{e14651d5e9644470b83d65f823c8bc85,
title = "Consequences of intraventricular hemorrhage in a rabbit pup model",
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.",
keywords = "Germinal matrix hemorrhageintraventricular hemorrhage, Gliosis, Myelin, Neurobehavioral testing, Ventriculomegaly, White matter",
author = "Chua, {Caroline O.} and Halima Chahboune and Alex Braun and Krishna Dummula and Chua, {Charles Edrick} and Jen Yu and Zoltan Ungvari and Sherbany, {Ariel A.} and Fahmeed Hyder and Praveen Ballabh",
year = "2009",
month = "10",
doi = "10.1161/STROKEAHA.109.549212",
language = "English (US)",
volume = "40",
pages = "3369--3377",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

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 -