title: Traumatic brain injury in mice deficient in poly-ADP(ribose) polymerase: a preliminary report.
abstract: Poly (ADP-ribose) polymerase (PARP) is a ubiquitous nuclear enzyme that, when activated by free-radical induced DNA damage, contributes to energy failure and cell death in models of central nervous system ischemia and reperfusion. PARP contributes to neuronal cell death in vivo after cerebral ischemia/reperfusion, however, the role of PARP in the pathogenesis of traumatic brain injury (TBI) is unknown. We hypothesized that, compared to wild type mice (+/+), mice deficient in PARP (-/-) would have reduced motor and cognitive deficits after TBI. Mice underwent controlled cortical impact (CCI) (6 m/s, 1.2 mm depth) and were tested for motor (d 1-5) and cognitive (d 14-18) function after CCI. PARP -/- mice demonstrated improved motor performance and improved cognitive function after CCI (both p < 0.05 compared to +/+). This is the first study to evaluate a role for PARP in functional outcome after TBI. The results suggest a detrimental role for PARP in the pathogenesis of TBI.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Whalen
authors.forename: R S
authors.initials: RS
authors.lastname: Clark
authors.forename: C E
authors.initials: CE
authors.lastname: Dixon
authors.forename: P
authors.initials: P
authors.lastname: Robichaud
authors.forename: D W
authors.initials: DW
authors.lastname: Marion
authors.forename: V
authors.initials: V
authors.lastname: Vagni
authors.forename: S
authors.initials: S
authors.lastname: Graham
authors.forename: L
authors.initials: L
authors.lastname: Virag
authors.forename: G
authors.initials: G
authors.lastname: Hasko
authors.forename: R
authors.initials: R
authors.lastname: Stachlewitz
authors.forename: C
authors.initials: C
authors.lastname: Szabo
authors.forename: P M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000503:physiopathology; D001929:Brain Edema / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D002470:Cell Survival / Q000502:physiology; D005625:Frontal Lobe / Q000098:blood supply / Q000293:injuries; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009048:Motor Skills / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology
chemical_list: D011065:Poly(ADP-ribose) Polymerases