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Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865., (© 2017 AlphaMed Press.)

The subventricular zone of the lateral ventricles (SVZ) is the largest source of neural stem cells (NSCs) in the adult mammalian brain. Newly generated neuroblasts from the SVZ form cellular chains that migrate through the rostral migratory stream (RMS) into the olfactory bulb (OB), where they become mature neurons. Migration through the RMS is a highly regulated process of intrinsic and extrinsic factors, orchestrated to achieve direction and integration of neuroblasts into OB circuitry. These factors include internal cytoskeletal and volume regulators, extracellular matrix proteins, and chemoattractant and chemorepellent proteins. All these molecules direct the cells away from the SVZ, through the RMS, and into the OB guaranteeing their correct integration. Following brain injury, some neuroblasts escape the RMS and migrate into the lesion site to participate in regeneration, a phenomenon that is also observed with brain tumors. This review focuses on factors that regulate the migration of SVZ precursor cells in the healthy and pathologic brain. A better understanding of the factors that control the movement of newly generated cells may be crucial for improving the use of NSC-replacement therapy for specific neurological diseases.

Neurogenesis persists in the adult subventricular zone (SVZ) of the mammalian brain. During aging, the SVZ neurogenic capacity undergoes a progressive decline, which is attributed to a decrease in the population of neural stem cells (NSCs). However, the behavior of the NSCs that remain in the aged brain is not fully understood. Here we performed a comparative ultrastructural study of the SVZ niche of 2-month-old and 24-month-old male C57BL/6 mice, focusing on the NSC population. Using thymidine-labeling, we showed that residual NSCs in the aged SVZ divide less frequently than those in young mice. We also provided evidence that ependymal cells are not newly generated during senescence, as others studies suggest. Remarkably, both astrocytes and ependymal cells accumulated a high number of intermediate filaments and dense bodies during aging, resembling reactive cells. A better understanding of the changes occurring in the neurogenic niche during aging will allow us to develop new strategies for fighting neurological disorders linked to senescence.

Objective: There has been an increased focus on the region adjacent to the lateral ventricles (LV) as a potential source of malignant tumors and/or more aggressive disease. We set out to determine if glioblastoma multiforme (GBM) bordering the LV was associated with decreased survival as compared to non-LV GBM., Methods: We reviewed the clinical records of 69 consecutive patients undergoing craniotomy for GBM at a single academic institution. Twenty-six patients were identified with contrast-enhancing lesions (CEL) bordering the LV (LV CEL). These 26 patients were matched with 26 patients with CEL not bordering the LV (non-LV CEL). These cohorts were matched for factors consistently shown to be associated with survival, which were age, tumor size, Karnofsky performance score, extent of resection, Gliadel implantation, and Temodar chemotherapy. Overall survival was compared between the cohorts via Log-rank analysis., Results: Despite similarities in pre-operative clinical status, tumor size, peri-operative outcome, and treatment regimens, the median survival for patients with LV CEL was significantly decreased as compared to patients with non-LV CEL (8 months vs. 11 months), P = 0.02. Additionally, survival analysis in patients stratified by primary and secondary resection also demonstrated a strong trend towards decreased survival after resection of LV CEL. After primary and secondary resection, patients with LV CEL versus non-LV CEL had a median survival of 11 months vs. 14 months (P = 0.10) and 7 months vs. 10 months (P = 0.11), respectively., Conclusion: While the causal factors underlying this observation are not provided with this observational study, GBM bordering the LV may carry a prognostic significance.