James M. Hillis

Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis.

Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS‐induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin‐3 (Gal‐3), a proinflammatory protein. Gal‐3 expression was increased in periventricular regions of human MS in post‐mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theilers murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal‐3−/− mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal‐3−/− mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal‐3−/− mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal‐3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal‐3 plays a central role in modulating the SVZ neurogenic niches response to this model of MS. GLIA 2016;64:105–121

Cuprizone demyelination induces a unique inflammatory response in the subventricular zone

BackgroundCuprizone leads to demyelination of the corpus callosum (CC) and activates progenitor cells in the adjacent subventricular zone (SVZ), a stem cell niche which contributes to remyelination. The healthy SVZ contains semi-activated microglia and constitutively expresses the pro-inflammatory molecule galectin-3 (Gal-3) suggesting the niche uniquely regulates inflammation.MethodsWe studied the inflammatory response to cuprizone in the SVZ and CC in Gal-3 knockout mice using immunohistochemistry and with the in vitro neurosphere assay.ResultsCuprizone caused loss of myelin basic protein (MBP) immunofluorescence in the CC suggesting demyelination. Cuprizone increased the density of CD45+/Iba1+ microglial cells and also increased Gal-3 expression in the CC. Surprisingly, the number of Gal-3+ and CD45+ cells decreased in the SVZ after cuprizone, suggesting inflammation was selectively reduced therein. Inflammation can regulate SVZ proliferation and indeed the number of phosphohistone H3+ (PHi3+) cells decreased in the SVZ but increased in the CC in both genotypes after cuprizone treatment. BrdU+ SVZ cell numbers also decreased in the SVZ after cuprizone, and this effect was significantly greater at 3xa0weeks in Gal-3−/− mice compared to WT, suggesting Gal-3 normally limits SVZ cell emigration following cuprizone treatment.ConclusionsThis study reveals a uniquely regulated inflammatory response in the SVZ and shows that Gal-3 participates in remyelination in the cuprizone model. This contrasts with more severe models of demyelination which induce SVZ inflammation and suggests the extent of demyelination affects the SVZ neurogenic response.

Teaching the Neurological Examination in a Rapidly Evolving Clinical Climate

Abstract The neurological examination remains the essence of neurology. It allows symptoms to be assessed, diagnoses to be made, and dynamic functions to be followed. Skill in the neurological examination has faced increasing challenges from the encroachment of diagnostic imaging, but has maintained its clinical utility. It has also encountered the battle for the precious time within a medical curriculum. This review considers how the neurological examination can best be taught into the future. It does so by considering factors related to the examination, the learner, the teacher, and the modern clinical environment.

Neurology Training Worldwide

Abstract Neurology training is essential for providing neurologic care globally. Large disparities in availability of neurology training exist between higher‐ and lower‐income countries. This review explores the worldwide distribution of neurology training programs and trainees, the characteristics of training programs in different parts of the world, and initiatives aimed at increasing access to neurology training in under‐resourced regions.