Tibial plateau angle in four common canine breeds with cranial cruciate ligament rupture, and its relationship to meniscal tears.

OBJECTIVES: To compare tibial plateau angle (TPA) among Labrador Retrievers, Rottweilers, Boxers, and German Shepherd Dogs that had undergone tibial plateau leveling osteotomies (TPLO) for cranial cruciate ligament disease, and to determine if higher TPAs are associated with increased risk for concurrent meniscal injury. METHODS: This was a retrospective study including 275 client-owned dogs of one of the four aforementioned breeds that received TPLO radiographs between 1999 and 2005 prior to undergoing the TPLO procedure. The TPA measured by the original surgeon was compared among four breeds and analyzed with respect to presence or absence of meniscal injury diagnosed via arthroscopy or arthrotomy at the time of surgery. RESULTS: Labrador Retrievers, Rottweilers, Boxers, and German Shepherd Dogs had mean TPAs of 25.9 degrees , 26.2 degrees , 25.9 degrees , and 28.2 degrees , respectively. The TPA of German Shepherd Dogs was significantly higher than that of the other breeds of dogs examined. TPA higher than the mean for dogs in this study did not significantly increase the risk for concurrent meniscal injury. CLINICAL SIGNIFICANCE: German Shepherd Dogs with cranial cruciate ligament disease had a significantly higher TPA compared to the other breeds examined. Higher TPA did not increase the likelihood of meniscal tears in this study. However, several variables that were not assessed, including the degree of cranial cruciate ligament integrity at the time of surgery and the time between original CrCL deficiency and surgical assessment, could have affected this analysis.

NMDA but not non-NMDA excitotoxicity is mediated by Poly(ADP-ribose) polymerase.

Poly(ADP-ribose) polymerase (PARP-1), a nuclear enzyme that facilitates DNA repair, may be instrumental in acute neuronal cell death in a variety of insults including, cerebral ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, and CNS trauma. Excitotoxicity is thought to underlie these and other toxic models of neuronal death. Different glutamate agonists may trigger different downstream pathways toward neurotoxicity. We examine the role of PARP-1 in NMDA- and non-NMDA-mediated excitotoxicity. NMDA and non-NMDA agonists were stereotactically delivered into the striatum of mice lacking PARP-1 and control mice in acute (48 hr) and chronic (3 week) toxicity paradigms. Mice lacking PARP-1 are highly resistant to the excitoxicity induced by NMDA but are as equally susceptible to AMPA excitotoxicity as wild-type mice. Restoring PARP-1 protein in mice lacking PARP-1 by viral transfection restored susceptibility to NMDA, supporting the requirement of PARP-1 in NMDA neurotoxicity. Furthermore, Western blot analyses demonstrate that PARP-1 is activated after NMDA delivery but not after AMPA administration. Consistent with the theory that nitric oxide (NO) and peroxynitrite are prominent in NMDA-induced neurotoxicity, PARP-1 was not activated in mice lacking the gene for neuronal NO synthase after NMDA administration. These results suggest a selective role of PARP-1 in glutamate excitoxicity, and strategies of inhibiting PARP-1 in NMDA-mediated neurotoxicity may offer substantial acute and chronic neuroprotection.

Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson's disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-ribose) polymerase (PARP), which catalyzes the attachment of ADP ribose units from NAD to nuclear proteins after DNA damage, are dramatically spared from MPTP neurotoxicity. MPTP potently activates PARP exclusively in vulnerable dopamine containing neurons of the substantia nigra. MPTP elicits a novel pattern of poly(ADP-ribosyl)ation of nuclear proteins that completely depends on neuronally derived nitric oxide. Thus, NO, DNA damage, and PARP activation play a critical role in MPTP-induced parkinsonism and suggest that inhibitors of PARP may have protective benefit in the treatment of Parkinson's disease.