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Regionally distinct patterns of calpain activation and traumatic axonal injury following contusive brain injury in immature rats
Journal article   Peer reviewed

Regionally distinct patterns of calpain activation and traumatic axonal injury following contusive brain injury in immature rats

Jimmy W Huh, Michael A Franklin, Ashley G Widing and Ramesh Raghupathi
Developmental neuroscience, v 28(4-5), pp 466-476
2006
PMID: 16943669

Abstract

Dendrites - pathology Calpain - metabolism Diffuse Axonal Injury - physiopathology Nerve Degeneration - physiopathology Brain Injuries - metabolism Brain Injuries - physiopathology Nerve Degeneration - metabolism Brain - metabolism Cerebral Infarction - physiopathology Cerebral Infarction - metabolism Up-Regulation - physiology Amyloid beta-Protein Precursor - metabolism Disease Models, Animal Animals, Newborn Dendrites - metabolism Brain - physiopathology Axons - metabolism Rats Diffuse Axonal Injury - etiology Animals Aging - physiology Cell Death - physiology Axons - pathology Biomarkers Brain - pathology Cerebral Infarction - etiology Nerve Degeneration - etiology
Impact-induced head injury in infants results in acute focal contusions and traumatic axonal injury (TAI) that are associated with chronic holohemispheric cortical and white matter atrophy and may contribute to poor outcome in brain-injured children less than 4 years of age. Contusive brain trauma in postnatal day (PND) 11 or PND 17 rat pups, ages neurologically equivalent to a human infant and toddler, respectively, leads to cortical tissue loss and white matter atrophy which are associated with cognitive deficits. In adult models of brain trauma and in brain-injured humans, acute and sustained activation of the calpain family of calcium-activated neutral proteases has been implicated in neuronal death and TAI. PND 11 or PND 17 rat pups were subjected to closed head injury over the left hemisphere using the controlled cortical impact device and sacrificed at 6 h, 24 h or 3 days. Hemorrhagic contusions and tissue tears in the cortex and white matter were visible at 6 h, and neuronal loss was evident by 3 days. Calpain activation was observed in cell soma and dendrites of injured neurons at 6 h, and in degenerating dendrites and atrophic neurons at 24 h after injury at both ages. Axonal accumulation of amyloid precursor protein, indicative of TAI, was observed in the corpus callosum and lateral aspects of the white matter below the site of impact, and in the thalamus in PND 11 rats only. Intra-axonal calpain activation was observed to a limited extent in the corpus callosum and subcortical white matter tracts in both brain-injured PND 11 and PND 17 rats. Collectively, these results provide evidence that calpain activation may participate in neuronal loss in the injured cortex, but may not contribute to the pathogenesis of TAI following contusive brain trauma in the immature rat.

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Collaboration types
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Web of Science research areas
Developmental Biology
Neurosciences
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