Neural stem cells (NSCs) in the postnatal mammalian brain self-renew and are a source of neurons and glia. To date, little is known about the molecular and cellular mechanisms regulating the maintenance and differentiation of these multipotent progenitors. We show that Jagged1 is required by mitotic cells in the subventricular zone (SVZ) and stimulates self-renewal of multipotent epidermal growth factor-dependent NSCs. Jagged1-expressing cells line the adult SVZ and are juxtaposed to Notch1-expressing cells, some of which are putative NSCs. In vitro, endogenous Jagged1 acts through Notch1 to promote NSC maintenance and multipotency. In vivo, reducing Jagged1/Notch1 signaling decreases the number of proliferating cells in the SVZ. In addition, soluble Jagged1 promotes self-renewal and neurogenic potential of multipotent neural progenitors in vitro. Our findings suggest a central role for Jagged1 in the NSC niche in the SVZ for maintaining a population of NSCs in the postnatal brain.

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In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation.

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BackgroundMagnetic resonance imaging (MRI) is the standard neuroimaging method to diagnose neoplastic brain lesions, as well as to perform stereotactic biopsy surgical planning. MRI has the advantage of providing structural anatomical details with high sensitivity, though histological specificity is limited. Although combining MRI with other imaging modalities, such as positron-emission tomography (PET), has proven to increment specificity, exact correlation between PET threshold uptake ratios (URs) and histological diagnosis and grading has not yet been described.ObjectivesThe aim of this study was to correlate exactly the histopathological criteria of the biopsy site to its PET uptake value with high spatial resolution (mm3), and to analyze the diagnostic value of PET using the amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) PET in patients with newly diagnosed brain lesions in comparison to histological findings obtained from stereotactic serial biopsy.Patients and methodsA total of 23 adult patients with newly diagnosed brain tumors on MRI were enrolled in this study. Subsequently to diagnoses, all patients underwent a 18F-FET PET-guided stereotactic biopsy, using an original newly developed software module, which is presented here. Conventional MRI, stereotactic computed tomography series, and 18F-FET PET images were semiautomatically fused, and hot-spot detection was performed for target planning. UR was determined using the uptake value from the biopsy sites in relation to the contralateral frontal white matter. UR values ≥1.6 were considered positive for glioma. High-grade glioma (HGG) was suspected with URs ≥3.0, while low-grade glioma (LGG) was suspected with URs between 1.6 and 3.0. Stereotactic serial biopsies along the trajectory at multiple sites were performed in millimeter steps, and the FET URs for each site were correlated exactly with a panel of 27 different histopathological markers. Comparisons between FET URs along the biopsy trajectories and the histological diagnoses were made with Pearson product-moment correlation coefficients. Analysis of variance was performed to test for significant differences in maximum UR between different tumor grades.ResultsA total of 363 biopsy specimens were taken from 23 patients by stereotactic serial biopsies. Histological examination revealed eight patients (35%) with an LGG: one with a World Health Organization (WHO)-I lesion and seven with a WHO-II lesion. Thirteen (57%) patients revealed an HGG (two with a WHO-III and three with a WHO-IV tumor), and two patients (9%) showed a process that was neither HGG nor LGG (group X or no-grade group). The correlation matrix between histological findings and the UR revealed five strong correlations. Low cell density in tissue samples was found to have a significant negative correlation with the measured cortical uptake rate (r=−0.43, P=0.02), as well as moderate cell density (r=−0.48, P=0.02). Pathological patterns of proliferation (r=0.37, P=0.04), GFAP (r=0.37, P=0.04), and Olig2 (r=0.36, P=0.05) showed a s...