Epidemiology of the lymphatic-dwelling filarioid nematode Rumenfilaria andersoni in free-ranging moose (Alces alces) and other cervids of North America

Background: Moose (Alces alces) are a culturally and economically valued species in Minnesota, where the northeast population has decreased by 60 % since 2006. The cause of the decline is currently unclear; however, parasites, predation, and climate change have all been implicated. Nematode parasites are important pathogens in North American moose, potentially causing severe disease and mortality. Recent spread of Rumenfilaria andersoni, a filarioid nematode of moose, has been documented in Finnish cervids; however, little is known about the epidemiology of this parasite in North America. Methods: To investigate the prevalence and distribution of R. andersoni, 584 blood samples were collected from live-captured and dead animals and screened microscopically for the presence of microfilariae using a modified Knott's test. Microfilariae were identified based on morphological characteristics. A subset of Knott's-positive animals was subjected to polymerase chain reaction (PCR) with filarioid-specific primers targeting the first internal transcribed spacer region (ITS-1) of the rRNA gene cluster. Results: Rumenfilaria microfilariae were present in 20.5 % of Minnesota moose (n = 352), with slight fluctuations observed over four years. Minnesota white-tailed deer (Odocoileus virginianus) (n = 2) and moose (n = 44) from Alaska, Montana, Washington, Maine, and New Hampshire also harbored R. andersoni, suggesting this parasite occurs widely throughout North American moose herds, and white-tailed deer can serve as a patent host. Sequence analysis of cervid blood (moose, n = 15; white-tailed deer, n = 1) confirmed the identity of R. andersoni and revealed the existence of two distinct clades. Genetic comparisons of R. andersoni isolates from North America and semi-domesticated Finnish reindeer found the two groups to be closely related, supporting previous hypotheses that R. andersoni was recently introduced into Finland by the importation of deer from the United States. Conclusions: To the best of our knowledge these observations represent the first report of R. andersoni within the contiguous United States and reveal this nematode as a common parasite of North American moose and white-tailed deer. Although the implications of R. andersoni infection on moose health is unclear, increased awareness of this parasite will help prevent unintentional introduction of R. andersoni into naive populations via the translocation of wild and captive cervids.Peer reviewe

Blood Vitronectin Induces Detrimental Brain Interleukin-6 and Correlates With Outcomes After Stroke Only in Female Mice

Background and Purpose - Women have worse stroke outcomes than men, especially after menopause. Few studies have focused on female-specific mechanisms, other than hormones. We investigated the role of the blood protein VTN (vitronectin) after ischemic stroke in mice. Methods - Adult male and female VTN knockout and wild-type littermates and C57BL/6 mice received a middle cerebral artery occlusion and the injured brain tissue analyzed 24 hours to 3 weeks later for cell loss and inflammation, as well as neurological function. Blood VTN levels were measured before and after stroke. Results - Intravenously injected VTN leaked extensively from bloodstream into brain infarct and penumbra by 24 hours after stroke. Strikingly, VTN was detrimental in female, but not male, mice, as shown by reduced brain injury (26.2±2.6% versus 13.4±3.8%; P=0.018; n=6 and 5) and forelimb dysfunction in female VTN knockout mice. Stroke increased plasma VTN 2- to 8-fold at 24 hours in females (36±4 versus 145±24 μg/mL; P\u3c0.0001; n=10 and 7), but not males (62±8 versus 68±6; P\u3e0.99; n=10 and 7), and returned to control levels by 7 days. Individually variable VTN levels at 24 hours correlated with stroke-induced brain injury at 7 days only in females. VTN promoted stroke-induced microglia/macrophage activation and leukocyte infiltration in females. Proinflammatory IL (interleukin)-6 greatly increased in the striatum at 24 hours in wild-type mice but was increased ≈60% less in female (739±159 versus 268±111; P=0.02; n=7 and 6), but not male (889±178 versus 1179±295; P=0.73; n=10 and 11), knockout mice. In individual wild-type females, plasma VTN levels correlated with striatal IL-6 expression at 24 hours. The female-specific effect of VTN-induced IL-6 expression following stroke was not due to gonadal hormones, as shown by ovariectomy and castration. Lastly, intrastriatal injection of IL-6 in female mice immediately before stroke reversed the VTN knockout phenotypes of reduced brain injury and microglia/macrophage activation. Conclusions - VTN plays a novel sexually dimorphic detrimental pathophysiological role in females and might ultimately be a therapeutic target to improve stroke outcomes in women