Tissue Response to Deep Brain Stimulation and Microlesion: A Comparative Study.

OBJECTIVES: Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up-regulation of neural progenitor cell proliferation in post-mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, neural progenitor cells, and microglia. METHODS: We used naïve rats in this study for DBS electrode implantation, stimulation, and microlesions. We used immunohistochemistry techniques for labeling microglial and progenitor cells, and fluorescence microscopy for viewing and quantification of labeled cells. RESULTS: We present data that demonstrates a reciprocal relationship of microglia and neural precursor cells in the presence of acute high frequency stimulation. In our hands, stimulated animals demonstrate significantly lower numbers of activated microglia (p = 0.026) when compared to microlesion and sham animals. The subthalamic region surrounding the DBS stimulating electrode reveals a significant increase in the number of neural precursor cells expressing cell cycle markers, plasticity and precursor cell markers (Ki67; p = 0.0013, MCM2; p = 0.0002). INTERPRETATION: We conclude that in this animal model, acute DBS results in modest local progenitor cell proliferation and influenced the total number of activated microglia. This could be of clinical significance in patients with PD, as it is thought to progress via neuroinflammatory processes involving microglia, cytokines, and the complement system. Further studies are required to comprehend the behavior of microglia in different activation states and their ability to regulate adult neurogenesis under physiologic and pathologic conditions.

Polycystic ovary syndrome in adolescents.

Polycystic ovary syndrome (PCOS) typically manifests with a combination of menstrual dysfunction and evidence of hyperandrogenism in the adolescent population. No single cause has been identified; however, evidence suggests a complex interplay between genetic and environmental factors. Polycystic ovary syndrome presents a particular diagnostic challenge in adolescents as normal pubertal changes can present with a similar phenotype. Management of PCOS in the adolescent population should focus on a multi-modal approach with lifestyle modification and pharmacologic treatment to address bothersome symptoms. This chapter outlines the pathogenesis of PCOS, including the effects of obesity, insulin resistance, genetic, and environmental factors. The evolution of the diagnostic criteria of PCOS as well as specific challenges of diagnosis in the adolescent population are reviewed. Finally, evidence for lifestyle modification and pharmacologic treatments are discussed.