Continual reelin signaling by the prime neurogenic niche of the adult brain

During development reelin sets the pace of neocortical neurogenesis enabling in turn newborn neurons to migrate, but whether and, if so, how reelin signaling affects the adult neurogenic niches remains uncertain. We show that reelin signaling, resulting in Dab1 phosphorylation, occurs in the ependymal-subependymal zone (EZ/SEZ) of the lateral ventricles where, along with its associated rostral migratory stream (RMS), the highest density of functional ApoER2 accumulates. Mice deficient for reelin, ApoER2 or Dab1 exhibit enlarged ventricles and dysplastic RMS. Moreover, while the conditional ablation of Dab1 in neural progenitor cells (NPCs) enlarges the ventricles and impairs neuroblasts clearance from the SEZ, the transgenic misexpression of reelin in NPCs of reelin-deficient mice normalizes the ventricular lumen and the density of ependymal cilia, ameliorating in turn neuroblasts migration; consistently, intraventricular infusion of reelin reroutes neuroblasts. These results demonstrate that reelin signaling persists sustaining the germinal niche of the lateral ventricles and influencing neuroblasts migration in the adult brain.

Intraoperative Chemotherapy for Leptomeningeal Metastases After Ommaya Placement

IntroductionThere is a wide variety in the timing of the first intraventricular chemotherapy dose after Ommaya reservoir placement. Given the rapid nature of leptomeningeal metastasis, it is important to avoid any delays in treatment in order to have the optimal therapeutic benefit. We present the first series of immediate intraoperative intraventricular infusion of chemotherapy after Ommaya placement.MethodsA single-institution, retrospective review of twenty patients who underwent surgical placement of an Ommaya reservoir from 2012 to 2020 and had intraoperative infusion of chemotherapy was conducted. Inclusion criteria consisted of patients 18 years and older with a diagnosis of leptomeningeal metastases, central nervous system lymphoma or leukemia. Outcomes such as leukoencephalopathy, wound healing, intracranial hemorrhage, catheter malfunction, Ommaya days, mortality, and other complications were reviewed.ResultsThe mean patient age was 55.1 years and the most common diagnosis was breast cancer (40%). All catheters were placed into the ventricular system, and there were no wound healing complications, infections or symptomatic leukoencephalopathy. Intraventricular chemotherapy was administered for a total of 201 cycles and a mean of 10 times per patient. The number of Ommaya days ranged from 7 to 2177, with a mean of 326.5 days, and 30-day mortality was 10%.Conclusions Ommaya reservoirs are effective intraventricular delivery mechanism for chemotherapy in patients with leptomeningeal metastases. Endoscopy-assisted placement of Ommaya catheters provides a real-time, visual confirmation of adequate placement. Immediate intraoperative intraventricular infusion of chemotherapy after Ommaya placement is safe, effective, and may increase efficiency in time to treatment for patients.