Selective vulnerability of subplate neurons after early neonatal hypoxia-ischemia.
Neonatal hypoxia-ischemia in the preterm human leads to selective injury to the subcortical developing white matter, which results in periventricular leukomalacia (PVL), a condition associated with abnormal neurodevelopment. Maturation-dependent vulnerability of late oligodendrocyte progenitors is thought to account for the cellular basis of this condition. A high frequency of cognitive and sensory deficits with decreasing gestational age suggests pervasive abnormalities of cortical development. In a neonatal rat model of hypoxic-ischemic injury that produces the characteristic pattern of subcortical injury associated with human PVL, selective subplate neuron death is seen. The premature subplate neuron death occurs after thalamic axons have reached their targets in cortex. Thus, as expected, thalamocortical connections form normally, including patterned connections to somatosensory cortex. However, deficits in motor function still occur, as in babies with PVL. Subplate neuron cell death in PVL provides another mechanism for abnormal neurodevelopment after neonatal hypoxia-ischemia.
McQuillen
Patrick S
PS
Department of Pediatrics, University of California San Francisco Medical Center, San Francisco, California 94143-0106, USA. psmcq@itsa.ucsf.edu
Sheldon
R Ann
RA
Shatz
Carla J
CJ
Ferriero
Donna M
DM
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000254:growth & development / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000493:pharmacokinetics; D002452:Cell Count; D016923:Cell Death; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology*; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000209:etiology / Q000473:pathology*; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000473:pathology
D001973:Bromodeoxyuridine