title: Differential effects of FK506 on structural and functional axonal deficits after diffuse brain injury in the immature rat.
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.
authors.affiliation: Program in Neuroscience, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Ann Mae
authors.initials: AM
authors.lastname: Dileonardi
authors.forename: Jimmy W
authors.initials: JW
authors.lastname: Huh
authors.forename: Ramesh
authors.initials: R
authors.lastname: Raghupathi
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus