Traumatic injury to the immature brain results in progressive neuronal loss, hyperactivity and delayed cognitive impairments.
The immature brain may be particularly vulnerable to injury during critical periods of development. To address the biologic basis for this vulnerability, mice were subjected to traumatic brain injury at postnatal day 21, a time point that approximates that of the toddler-aged child. After motor and cognitive testing at either 2 weeks (juveniles) or 3 months (adults) after injury, animals were euthanized and the brains prepared for quantitative histologic assessment. Brain-injured mice exhibited hyperactivity and age-dependent anxiolysis. Cortical lesion volume and subcortical neuronal loss were greater in brain-injured adults than in juveniles. Importantly, cognitive decline was delayed in onset and coincided with loss of neurons in the hippocampus. Our findings demonstrate that trauma to the developing brain results in a prolonged period of pathogenesis in both cortical and subcortical structures. Behavioral changes are a likely consequence of regional-specific neuronal degeneration.
Pullela
Ramadevi
R
Department of Pediatrics, University of California, San Francisco, CA 94143-0520, USA.
Raber
Jacob
J
Pfankuch
Timothy
T
Ferriero
Donna M
DM
Claus
Catherine P
CP
Koh
Seong-Eun
SE
Yamauchi
Toshihiro
T
Rola
Radoslaw
R
Fike
John R
JR
Noble-Haeusslein
Linda J
LJ
D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology*; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D002658:Developmental Disabilities / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology; D011595:Psychomotor Agitation / Q000209:etiology / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013995:Time