Combined open microsurgical and endoscopic resection of hypothalamic hamartomas.

Hypothalamic hamartomas (HHs) are typically located within the vicinity of the third ventricle. They can be attached to the walls of the third ventricle, within the interpeduncular cistern (third ventricle floor), and/or attached to the mammillary bodies and hypothalamus. Depending on their location, resection is performed either through the third ventricle, approaching from above, or via a frontotemporal craniotomy (pterional or frontoorbital), approaching from below. "Above" approaches typically include the transcallosal-anterior interforniceal approach, and recently, purely endoscopic approaches performed transforaminally. The authors present a combined open and endoscopic approach for resection of HHs located within the third ventricle. They used this approach in 2 young girls with relatively small lateral and third ventricles. Following an interhemispheric, transcallosal approach and exposure of the right foramen of Monro, an endoscope was inserted through the foramen, which enabled safe resection of the HH. The main advantage of the combined approach is when the lateral and third ventricles are relatively small, making a purely endoscopic approach more challenging and possibly riskier.

Enhanced survival and neurite network formation of human umbilical cord blood neuronal progenitors in three-dimensional collagen constructs.

Umbilical cord blood (CB) stem cells have been proposed for cell-based therapeutic applications for diverse diseases of the CNS. We hypothesized that tissue-engineering strategies may extend the efficacy of these approaches by improving the long-term viability and function of stem cell-derived neuronal progenitors. To test our hypothesis, we explored the survival and differentiation of human CB-derived neuronal progenitors (HUCBNP) in a three-dimensional (3D) collagen construct. In contrast to two-dimensional culture conditions, the cells survived in 3D for an extended period of time of more than 2 months. Under 3D conditions, HUCBNP underwent spontaneous neuronal differentiation, which was further enhanced by treatment with neuronal conditioned medium (CM) and nerve growth factor (NGF). Neurite outgrowth, quantified by assessing the fractal dimension (D f) of the complex neuronal networks, was significantly enhanced under 3D conditions in the presence of CM/NGF, concomitant with a reduced expression of the early neuronal marker nestin (1.9-fold), and increased levels of mature neuronal markers such as MAP-2 (3.6-fold), ß-tubulin (1.5-fold), and neuronal specific enolase (6.6-fold) and the appearance of the synaptic marker synaptophysin. To assess the feasibility for clinical usage, HUCBNP were also isolated from frozen CB samples and cultured under 3D conditions. The data indicate the essential complete preservation of neurotrophic (survival) and neurotropic (neurite outgrowth) properties. In conclusion, 3D culture conditions are proposed as an essential step for both maintenance of CB neuronal progenitors in vitro and for investigating specific features of neuronal differentiation towards future use in regenerative therapy.

Neuroprotection by cord blood neural progenitors involves antioxidants, neurotrophic and angiogenic factors.

Human umbilical cord blood (HUCB) is a valuable source for cell therapy since it confers neuroprotection in stroke animal models. However, the responsible sub-populations remain to be established and the mechanisms involved are unknown. To explore HUCB neuroprotective properties in a PC12 cell-based ischemic neuronal model, we used an HUCB mononuclear-enriched population of collagen-adherent cells, which can be differentiated in vitro into a neuronal phenotype (HUCBNP). Upon co-culture with insulted-PC12 cells, HUCBNP conferred approximately 30% neuroprotection, as evaluated by decreased lactate dehydrogenase and caspase-3 activities. HUCBNP decreased by 95% the level of free radicals in the insulted-PC12 cells, in correlation with the appearance of antioxidants, as measured by changes in the oxidation-reduction potential of the medium using cyclic-voltammetry. An increased level of nerve growth factor (NGF), vascular endothelial growth factor and basic fibroblast growth factor in the co-culture medium was temporally correlated with a -medium neuroprotection effect, which was partially abolished by heat denaturation. HUCBNP-induced neuroprotection was correlated with changes in gene expression of these neurotrophic factors, while blocked by K252a, an antagonist of the TrkA/NGF receptor. These findings indicate that HUCBNP-induced neuroprotection involves antioxidant(s) and neurotrophic factors, which, by paracrine and/or autocrine interactions between the insulted-PC12 and the HUCBNP cells, conferred neuroprotection.