PURPOSE: Pediatric traumatic brain injury (TBI) represents a prominent yet understudied medical condition that can profoundly impact brain development. As the juvenile injured brain matures in the wake of neuropathological cascades during potentially critical periods, circuit alterations may explain neurological consequences, including cognitive deficits. We hypothesize that experimental brain injury in juvenile rats, with behavioral deficits that resolve, will lead to quantifiable structural changes in hippocampal neurons at chronic time points post-injury. METHODS: Controlled cortical impact (CCI), a model of focal TBI with contusion, was used to induce brain injury on post-natal day (PND) 17 juvenile rats. The histological consequence of TBI was quantified in regions of the hippocampus at post-injury day 28 (PID28) on sections stained using a variation of the Golgi-Cox staining method. Individual neuronal morphologies were digitized from the dentate gyrus (DG), CA3, and CA1 regions. RESULTS: Soma area in the ipsilateral injured DG and CA3 regions of the hippocampus increased significantly at PID28 in comparison to controls. In CA1, dendritic length and dendritic branching decreased significantly in comparison to controls and the contralateral hemisphere, without change in soma area. To extend the study, we examined neuronal morphology in rats with CCI at PND7. On PID28 after CCI on PND7 rats, CA1 neurons showed no injury-induced change in morphology, potentially indicating an age-dependent morphological response to injury. CONCLUSIONS: Long-lasting structural alterations in hippocampal neurons of brain-injured PND17 juvenile animals, but not PND7 immature animals, suggest differential plasticity depending on age-at-injury, with potential consequences for later function.
PURPOSE: Pediatric traumatic brain injury (TBI) represents a prominent yet understudied medical condition that can profoundly impact brain development. As the juvenile injured brain matures in the wake of neuropathological cascades during potentially critical periods, circuit alterations may explain neurological consequences, including cognitive deficits. We hypothesize that experimental brain injury in juvenile rats, with behavioral deficits that resolve, will lead to quantifiable structural changes in hippocampal neurons at chronic time points post-injury. METHODS: Controlled cortical impact (CCI), a model of focal TBI with contusion, was used to induce brain injury on post-natal day (PND) 17 juvenile rats. The histological consequence of TBI was quantified in regions of the hippocampus at post-injury day 28 (PID28) on sections stained using a variation of the Golgi-Cox staining method. Individual neuronal morphologies were digitized from the dentate gyrus (DG), CA3, and CA1 regions. RESULTS: Soma area in the ipsilateral injured DG and CA3 regions of the hippocampus increased significantly at PID28 in comparison to controls. In CA1, dendritic length and dendritic branching decreased significantly in comparison to controls and the contralateral hemisphere, without change in soma area. To extend the study, we examined neuronal morphology in rats with CCI at PND7. On PID28 after CCI on PND7 rats, CA1 neurons showed no injury-induced change in morphology, potentially indicating an age-dependent morphological response to injury. CONCLUSIONS: Long-lasting structural alterations in hippocampal neurons of brain-injured PND17 juvenile animals, but not PND7 immature animals, suggest differential plasticity depending on age-at-injury, with potential consequences for later function.
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