title: Protective effects of zinc chelation in traumatic brain injury correlate with upregulation of neuroprotective genes in rat brain.
abstract: Chelation of excessive neuronal zinc ameliorates zinc neurotoxicity and reduces subsequent neuronal injury. To clarify the molecular mechanisms of this neuroprotective effect, we used a focused cDNA array of stress-response genes with zinc chelation (calcium EDTA) in our rat model of fluid percussion brain injury at 2 h, 24 h, and 7 days after injury. In parallel experiments, we compared neuronal cell death in TUNEL-stained brain sections in traumatized rats with and without calcium EDTA treatment. Zinc chelation induced the expression of several neuroprotective genes; neuroprotective gene expression correlated with substantially decreased numbers of TUNEL-positive cells.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0830, USA. hhellmic@utmb.edu
authors.forename: Helen L
authors.initials: HL
authors.lastname: Hellmich
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Frederickson
authors.forename: Douglas S
authors.initials: DS
authors.lastname: DeWitt
authors.forename: Ricardo
authors.initials: R
authors.lastname: Saban
authors.forename: Margaret O
authors.initials: MO
authors.lastname: Parsley
authors.forename: Rachael
authors.initials: R
authors.lastname: Stephenson
authors.forename: Marco
authors.initials: M
authors.lastname: Velasco
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Uchida
authors.forename: Megumi
authors.initials: M
authors.lastname: Shimamura
authors.forename: Donald S
authors.initials: DS
authors.lastname: Prough
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000378:metabolism* / Q000627:therapeutic use; D015913:Chelation Therapy / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D018696:Neuroprotective Agents; D015032:Zinc