Journal article
Differential effects of FK506 on structural and functional axonal deficits after diffuse brain injury in the immature rat
Journal of neuropathology and experimental neurology, v 71(11), pp 959-972
Nov 2012
PMID: 23095847
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Diffuse axonal injury is a major component of traumatic brain injury in children and correlates with long-term cognitive impairment. Traumatic brain injury in adult rodents has been linked to a decrease in compound action potential (CAP) in the corpus callosum, but information on trauma-associated diffuse axonal injury in immature rodents is limited. We investigated the effects of closed head injury on CAP in the corpus callosum of 17-day-old rats. The injury resulted in CAP deficits of both myelinated and unmyelinated fibers in the corpus callosum between 1 and 14 days postinjury (dpi). These deficits were accompanied by intra-axonal dephosphorylation of the 200-kDa neurofilament subunit (NF200) at 1 and 3 dpi, a decrease in total NF200 at 3 dpi and axonal degeneration at 3 and 7 dpi. Although total phosphatase activity decreased at 1 dpi, calcineurin activity was unchanged. The calcineurin inhibitor, FK506, significantly attenuated the injury-induced NF200 dephosphorylation of NF200 at 3 dpi and axonal degeneration at 3 and 7 dpi but did not affect the decrease in NF200 protein levels or impaired axonal transport. FK506 had no effect on CAP deficits at 3 dpi but exacerbated the deficit in only the myelinated fibers at 7 dpi. Thus, in contrast to adult animals, FK506 treatment did not improve axonal function in brain-injured immature animals, suggesting that calcineurin may not contribute to impaired axonal function.
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Details
- Title
- Differential effects of FK506 on structural and functional axonal deficits after diffuse brain injury in the immature rat
- Creators
- Ann Mae Dileonardi - Program in Neuroscience, Drexel University College of Medicine, Philadelphia, PA, USAJimmy W HuhRamesh Raghupathi
- Publication Details
- Journal of neuropathology and experimental neurology, v 71(11), pp 959-972
- Publisher
- Lippincott; England
- Grant note
- R01 HD061963 / NICHD NIH HHS K08 NS053651 / NINDS NIH HHS R01-HD061963 / NICHD NIH HHS K08-NS053651 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000310544800003
- Scopus ID
- 2-s2.0-84871207818
- Other Identifier
- 991014878413404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pathology