Interferon gamma protects neonatal neural stem/progenitor cells during measles virus infection of the brain.

BACKGROUND: In the developing brain, self-renewing neural stem/progenitor cells (NSPC) give rise to neuronal and glial lineages. NSPC survival and differentiation can be altered by neurotropic viruses and by the anti-viral immune response. Several neurotropic viruses specifically target and infect NSPCs, in addition to inducing neuronal loss, which makes it difficult to distinguish between effects on NSPCs that are due to direct viral infection or due to the anti-viral immune response. METHODS: We have investigated the impact of anti-viral immunity on NSPCs in measles virus (MV)-infected neonates. A neuron-restricted viral infection model was used, where NSPCs remain uninfected. Thus, an anti-viral immune response was induced without the confounding issue of NSPC infection. Two-transgenic mouse lines were used: CD46+ mice express the human isoform of CD46, the MV entry receptor, under the control of the neuron-specific enolase promoter; CD46+/IFNγ-KO mice lack the key anti-viral cytokine IFNγ. Multi-color flow cytometry and Western Blot analysis were used to quantify effects on NSPC, neuronal, and glial cell number, and quantify effects on IFNγ-mediated signaling and cell markers, respectively. RESULTS: Flow cytometric analysis revealed that NSPCs were reduced in CD46+/IFNγ-KO mice at 3, 7, and 10 days post-infection (dpi), but were unaffected in CD46+ mice. Early neurons showed the greatest cell loss at 7 dpi in both genotypes, with no effect on mature neurons and glial cells. Thus, IFNγ protected against NSPC loss, but did not protect young neurons. Western Blot analyses on hippocampal explants showed reduced nestin expression in the absence of IFNγ, and reduced doublecortin and ßIII-tubulin in both genotypes. Phosphorylation of STAT1 and STAT2 occurred independently of IFNγ in the hippocampus, albeit with distinct regulation of activation. CONCLUSIONS: This is the first study to demonstrate bystander effects of anti-viral immunity on NSPC function. Our results show IFNγ protects the NSPC population during a neonatal viral CNS infection. Significant loss of NSPCs in CD46+/IFNγ-KO neonates suggests that the adaptive immune response is detrimental to NSPCs in the absence of IFNγ. These results reveal the importance and contribution of the anti-viral immune response to neuropathology and may be relevant to other neuroinflammatory conditions.

Medication Use Among Patients Prior to Bariatric Surgery.

Purpose: The aims of this study were to describe the most common medications reported by candidates for weight loss surgery and to consider the potential implications for patient care. Methods: A secondary data analysis of data from bariatric surgery patients enrolled in a randomized, controlled trial. At study entry, participants recorded their use of prescription medications they had taken in the previous 90 days. The Anatomical Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) Index 2014 was used to classify medications. Results: Participants (n=265) were 85.7% female and 83.0% white. Mean body mass index was 47.9±6.5 kg/m2, and age was 45.1±11 years. The average number of medications was 4.4±4.1, and the median was 3. The top three anatomical main groups were the cardiovascular system, alimentary tract and metabolism, and nervous system (28.2%, 21.6%, and 21.3% of all medications, respectively). The top therapeutic subgroups were drugs used in diabetes, psychoanaleptics, and agents acting on the renin-angiotensin system (12%, 11.3%, and 8.2% of all medications, respectively). Conclusions: Candidates for weight loss surgery report taking medications associated with obesity-related comorbidities such as diabetes, depression, and hypertension. Although many may be able to eliminate these medications, others will require close monitoring and dosage adjustment after surgery.