Annals of neurology
-
Annals of neurology · Feb 2013
Recombinant ADAMTS13 reduces tissue plasminogen activator-induced hemorrhage after stroke in mice.
Tissue plasminogen activator (tPA) is approved for treatment of acute ischemic stroke, but it increases the risk of cerebral hemorrhage. Accumulating evidence suggests that von Willebrand factor (VWF) plays a pivotal role in thrombus formation and microcirculatory disturbances after ischemic stroke. By cleaving VWF, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) protects mice from stroke. Therefore, we hypothesized that recombinant ADAMTS13 (rADAMTS13) could increase the safety of tPA thrombolysis in stroke. ⋯ These findings demonstrate that the VWF-cleaving protease rADAMTS13 reduced tPA-induced hemorrhage by regulating BBB integrity, and suggest that this effect may occur through the Akt/RhoA-mediated VEGF pathways.
-
Annals of neurology · Feb 2013
Matrix metalloproteinase 3 deletion preserves denervated motor endplates after traumatic nerve injury.
Traumatic peripheral nerve injuries often produce permanent functional deficits despite optimal surgical and medical management. One reason for the impaired target organ reinnervation is degradation of motor endplates during prolonged denervation. Here we investigate the effect of preserving agrin on the stability of denervated endplates. Because matrix metalloproteinase 3 (MMP3) is known to degrade agrin, we examined the changes in endplate structure following traumatic nerve injury in MMP3 knockout mice. ⋯ These results demonstrate a critical role for MMP3 in motor endplate remodeling, and reveal a potential target for therapeutic intervention to prevent motor endplate degradation following nerve injury.
-
Annals of neurology · Jan 2013
Randomized Controlled Trial Multicenter StudyPredictors of long-term outcome in multiple sclerosis patients treated with interferon β.
To identify early predictors of long-term outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) treated with intramuscular (IM) interferon beta-1a (IFNβ-1a). ⋯ Disease activity despite treatment with IFNβ is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFNβ-treated patients with MRI, and for changing therapy in patients with active disease.
-
Annals of neurology · Jan 2013
Genetic variants in the immunoglobulin heavy chain locus are associated with the IgG index in multiple sclerosis.
Intrathecal synthesis of immunoglobulin gamma (IgG) synthesis is frequently observed in patients with multiple sclerosis (MS). Whereas the extent of intrathecal IgG synthesis varies largely between patients, it remains rather constant in the individual patient over time. The aim of this study was to identify common genetic variants associated with the IgG index as a marker of intrathecal IgG synthesis in MS. ⋯ The extent of intrathecal IgG in MS is influenced by the IGHC locus. No association with susceptibility to MS was found. Therefore GM haplotypes might affect intrathecal IgG synthesis independently of the underlying disease.