Traumatic injury to the immature brain results in progressive neuronal loss, hyperactivity and delayed cognitive impairments

Dev Neurosci. 2006;28(4-5):396-409. doi: 10.1159/000094166.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Brain / growth & development
  • Brain / pathology*
  • Brain / physiopathology*
  • Brain Injuries / complications
  • Brain Injuries / physiopathology*
  • Cell Death / physiology
  • Cell Differentiation / physiology
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology*
  • Developmental Disabilities / etiology
  • Developmental Disabilities / physiopathology*
  • Disease Models, Animal
  • Disease Progression
  • Exploratory Behavior / physiology
  • Hippocampus / growth & development
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Infant
  • Male
  • Memory Disorders / etiology
  • Memory Disorders / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Nerve Degeneration / etiology
  • Nerve Degeneration / physiopathology*
  • Neurons / pathology
  • Psychomotor Agitation / etiology
  • Psychomotor Agitation / physiopathology*
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Time