TY - JOUR
T1 - Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats
AU - Robinson, Shenandoah
AU - Petelenz, Kasia
AU - Li, Qing
AU - Cohen, Mark L.
AU - DeChant, Anne
AU - Tabrizi, Nanor
AU - Bucek, Marik
AU - Lust, David
AU - Miller, Robert H.
N1 - Funding Information:
This work was supported by March of Dimes Foundation Award #5-FY00-603 to S.R. and NIH #NS 41093 and 36675 to R.H.M.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Cerebral palsy
KW - Cytokines
KW - Development
KW - Ischemia
KW - Oligodendrocyte
KW - Periventricular leukomalacia
KW - Prematurity
KW - White matter lesions
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U2 - 10.1016/j.nbd.2004.10.024
DO - 10.1016/j.nbd.2004.10.024
M3 - Article
C2 - 15755683
AN - SCOPUS:14744292269
SN - 0969-9961
VL - 18
SP - 568
EP - 581
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -