Poly(ADP-ribose) polymerase-1 and its clinical applications in brain injury.
Traumatic brain injury (TBI) is a devastating occurrence that may result in short- and long-term complications. Oxidative stress (an imbalance between oxidants and antioxidants) plays a critical role in the development of secondary injuries following TBI and, consequently, in patient outcomes. Secondary injuries resulting from oxidative stress produce DNA strand breaks that activate poly(adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) and produce another level of injury. PARP-1 functions as a DNA-damage sensor and signaling molecule. In response to the severe DNA damage after brain injury, PARP-1 becomes overactivated and depletes the cells' energy sources, which leads to cellular and neuronal death. Recently, PARP-1 inhibition has been studied in various animal models of brain injury with promising results. TBI treatments based on PARP-1 inhibition in humans are far from the clinical arena, although descriptive studies of PARP-1 activation in humans are beginning to emerge. Nurses should become involved in this area of collaborative research in human response to brain injury by helping design and implement safe and meaningful clinical trials.
Barr
Taura L
TL
National Institute of Nursing Research, Bethesda, MD, USA. barrt@mail.nih.gov
Conley
Yvette P
YP
D017209:Apoptosis; D001930:Brain Injuries / Q000150:complications / Q000201:enzymology* / Q000276:immunology / Q000628:therapy*; D002986:Clinical Trials as Topic; D003422:Critical Care / Q000379:methods; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D005609:Free Radicals / Q000009:adverse effects; D006301:Health Services Needs and Demand; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D024802:Nurse's Role; D009730:Nursing Assessment; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D017410:Practice Guidelines as Topic
D005609:Free Radicals; D047908:Intracellular Signaling Peptides and Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases