Protective effects of zinc chelation in traumatic brain injury correlate with upregulation of neuroprotective genes in rat brain.
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.
Hellmich
Helen L
HL
Department of Anesthesiology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0830, USA. hhellmic@utmb.edu
Frederickson
Christopher J
CJ
DeWitt
Douglas S
DS
Saban
Ricardo
R
Parsley
Margaret O
MO
Stephenson
Rachael
R
Velasco
Marco
M
Uchida
Tatsuo
T
Shimamura
Megumi
M
Prough
Donald S
DS
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*
D002614:Chelating Agents; D018696:Neuroprotective Agents; D015032:Zinc