title: Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats.
abstract: In infants, a common consequence of systemic perinatal insults is disruption of neonatal brain development. Such insults can cause cerebral palsy, cognitive delay, epilepsy and other chronic neurologic deficits in children. The mechanisms underlying disruption of brain development after perinatal insults are poorly defined. To mimic human systemic insults, a transient prenatal hypoxic-ischemic insult model was developed in rodents. Ischemic animals showed reproducible histological lesions including oligodendrocyte loss, gliosis, and axonal disruption. Ischemic animals displayed persistent postnatal loss of oligodendrocyte lineage cells and cortical neurons, decreased cell proliferation, increased cell death, elevated pro-inflammatory cytokine levels, and impaired motor skills as young adults. Progressive ischemic intervals produced a graded pattern of injury. This systemic rodent prenatal hypoxic-ischemic insult accurately models human perinatal brain injury in several important criteria, including functional association of altered brain development with motor delay, and consequently provides novel insights into the pathogenesis of human perinatal brain insults.
authors.affiliation: Department of Neurological Surgery, Case Research Institute, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. shenandoah.robinson@uhhs.com
authors.forename: Shenandoah
authors.initials: S
authors.lastname: Robinson
authors.forename: Kasia
authors.initials: K
authors.lastname: Petelenz
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Mark L
authors.initials: ML
authors.lastname: Cohen
authors.forename: Anne
authors.initials: A
authors.lastname: Dechant
authors.forename: Nanor
authors.initials: N
authors.lastname: Tabrizi
authors.forename: Marik
authors.initials: M
authors.lastname: Bucek
authors.forename: David
authors.initials: D
authors.lastname: Lust
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology*; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases