Explore the vast range of titles available.

The primate cerebrum is characterized by a large expansion of cortical surface area, the formation of convolutions, and extraordinarily voluminous subcortical white matter. It was recently proposed that this expansion is primarily driven by increased production of superficial neurons in the dramatically enlarged outer subventricular zone (oSVZ). Here, we examined the development of the parietal cerebrum in macaque monkey and found that, indeed, the oSVZ initially adds neurons to the superficial layers II and III, increasing their thickness. However, as the oSVZ grows in size, its output changes to production of astrocytes and oligodendrocytes, which in primates outnumber cerebral neurons by a factor of three. After the completion of neurogenesis around embryonic day (E) 90, when the cerebrum is still lissencephalic, the oSVZ enlarges and contains Pax6⁺/Hopx⁺ outer (basal) radial glial cells producing astrocytes and oligodendrocytes until after E125. Our data indicate that oSVZ gliogenesis, rather than neurogenesis, correlates with rapid enlargement of the cerebrum and development of convolutions, which occur concomitantly with the formation of cortical connections via the underlying white matter, in addition to neuronal growth, elaboration of dendrites, and amplification of neuropil in the cortex, which are primary factors in the formation of cerebral convolutions in primates.

Recent studies have highlighted the intricate relationship between cerebrospinal fluid (CSF) dynamics and global brain activity, suggesting a role in neurovascular coupling and brain waste clearance. The lateral ventricles are believed to play a key role in linking global BOLD (gBOLD) signals to CSF inflow (CSF in ) to the fourth ventricle. In this study, we developed a method to reliably quantify lateral ventricle volume (LVV) in fMRI data. Using three independent datasets, including resting-state and task-based fMRI, we assessed dynamic changes in LVV and their associations with gBOLD and CSF in . Our findings reveal a strong anti-correlation between LVV and gBOLD across all datasets, with an average gBOLD lag of approximately 1 s. The derivative of the LVV time series were positively correlated with CSF in , with CSF in lagging LVV changes by 1.4–2.4 s. A moderate negative correlation was also observed between CSF in and gBOLD, consistent with prior research. These results support the hypothesis that LVV fluctuations, driven by global cerebral blood volume oscillations, regulate CSF movement into and out of the fourth ventricle. Our findings provide a foundation for further investigations into the role of LVV dynamics in aging and neurological disorders.

Quantitative magnetic resonance analysis often requires accurate, robust, and reliable automatic extraction of anatomical structures. Recently, template-warping methods incorporating a label fusion strategy have demonstrated high accuracy in segmenting cerebral structures. In this study, we propose a novel patch-based method using expert manual segmentations as priors to achieve this task. Inspired by recent work in image denoising, the proposed nonlocal patch-based label fusion produces accurate and robust segmentation. Validation with two different datasets is presented. In our experiments, the hippocampi of 80 healthy subjects and the lateral ventricles of 80 patients with Alzheimer's disease were segmented. The influence on segmentation accuracy of different parameters such as patch size and number of training subjects was also studied. A comparison with an appearance-based method and a template-based method was also carried out. The highest median kappa index values obtained with the proposed method were 0.884 for hippocampus segmentation and 0.959 for lateral ventricle segmentation. ►The Nonlocal means estimator can be used to accurately segment anatomical brain structures such as hippocampus and lateral ventricles. ►Contrary to template warping methods working at the structure level, the proposed method handles a finer scale by using patches. ►Nonlocal patch-based segmentation does not require nonlinear registrations while providing state-of-the-art results.

Abstract BACKGROUND Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes. OBJECTIVE To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients. METHODS Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation). RESULTS Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact—but not ventricular entry—associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P < .001), and OS (HR 1.90 [1.35-2.67], P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted. CONCLUSION SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.

Intraventricular tumors frequently provoke alterations in ventricular morphology. This study aims to quantificational assess perioperative dynamic fluctuations in the cerebrospinal fluid (CSF) volume within the lateral ventricles of patients harboring lateral ventricular tumors. A retrospective review encompassing 90 patients who underwent surgical intervention for lateral ventricular tumors at our institution was undertaken. Comprehensive observations at multiple perioperative time points were conducted, and LVCV analyses were performed to delineate the longitudinal dynamic alterations in ventricular morphology. Additionally, LVCV measurements were juxtaposed with data from 19 healthy subjects to stratify patients into two cohorts: those exhibiting preoperative increased LVCV and those without such changes. After surgical excision of intraventricular tumors, alterations in LVCV were compared between these cohorts, with a factor analysis undertaken specifically among patients demonstrating increased LVCV to elucidate potential influencing variables. 40 patients (44.4%) diagnosed with intraventricular tumors presenting with enlarged preoperative LVCV [74.6 (49.3–101.8) cm 3 ] compared with the normal subject group, and the LVCV demonstrated a significant postoperative [41.3 (27.6–67.5) cm 3 ] reduction in 3 months ( p  < 0.001). Meanwhile, 50 patients (55.6%) without LVCV enlargement [14.5 (8.1–21.0) cm 3 ] experienced a notable increase following surgery in 3 months [20.2 (14.1–33.3) cm 3 , p  = 0.002]. Preoperative increased LVCV is an important factor leading to the increased LVCV postoperatively ( p  = 0.022, OR = 26.239), however, compared to healthy subjects, both groups exhibited a trend toward normalization of LVCV value postoperatively ( p  = 0.165, p  = 0.072, respectively). Following appropriate surgical excision of the tumor, the preoperative increased LVCV associated with intraventricular tumors does not hinder the normalization trend of ventricular morphology. Not all ventricular dilation requires preventive long-term external ventricular drainage and aggressive ventriculoperitoneal shunt treatment.

Galectin-3 (Gal-3) is an evolutionarily conserved and multifunctional protein that drives inflammation in disease. Gal-3’s role in the central nervous system has been less studied than in the immune system. However, recent studies show it exacerbates Alzheimer’s disease and is upregulated in a large variety of brain injuries, while loss of Gal-3 function can diminish symptoms of neurodegenerative diseases such as Alzheimer’s. Several novel molecular pathways for Gal-3 were recently uncovered. It is a natural ligand for TREM2 (triggering receptor expressed on myeloid cells), TLR4 (Toll-like receptor 4), and IR (insulin receptor). Gal-3 regulates a number of pathways including stimulation of bone morphogenetic protein (BMP) signaling and modulating Wnt signalling in a context-dependent manner. Gal-3 typically acts in pathology but is now known to affect subventricular zone (SVZ) neurogenesis and gliogenesis in the healthy brain. Despite its myriad interactors, Gal-3 has surprisingly specific and important functions in regulating SVZ neurogenesis in disease. Gal-1, a similar lectin often co-expressed with Gal-3, also has profound effects on brain pathology and adult neurogenesis. Remarkably, Gal-3’s carbohydrate recognition domain bears structural similarity to the SARS-CoV-2 virus spike protein necessary for cell entry. Gal-3 can be targeted pharmacologically and is a valid target for several diseases involving brain inflammation. The wealth of molecular pathways now known further suggest its modulation could be therapeutically useful.

Tissir et al . find that atypical cadherins Celsr2 and 3 and planar cell polarity signaling are required for the proper development and function of cilia in ependymal cells, and that their loss of function markedly impairs cerebrospinal fluid circulation. Ependymal cells form the epithelial lining of cerebral ventricles. Their apical surface is covered by cilia that beat in a coordinated fashion to facilitate circulation of the cerebrospinal fluid (CSF). The genetic factors that govern the development and function of ependymal cilia remain poorly understood. We found that the planar cell polarity cadherins Celsr2 and Celsr3 control these processes. In Celsr2 -deficient mice, the development and planar organization of ependymal cilia are compromised, leading to defective CSF dynamics and hydrocephalus. In Celsr2 and Celsr3 double mutant ependyma, ciliogenesis is markedly impaired, resulting in lethal hydrocephalus. The membrane distribution of Vangl2 and Fzd3, two key planar cell polarity proteins, was disturbed in Celsr2 mutants, and even more so in Celsr2 and Celsr3 double mutants. Our findings suggest that planar cell polarity signaling is involved in ependymal cilia development and in the pathophysiology of hydrocephalus, with possible implications in other ciliopathies.

The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of the embryonic brain, self-renew and generate basal progenitors 1 that delaminate and settle in the subventricular zone in enlarged brain regions 2 . The length of time that cells stay in the subventricular zone is essential for controlling further amplification and fate determination. Here we show that the interphase centrosome protein AKNA has a key role in this process. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination. The interphase centrosome protein AKNA is necessary and sufficient for the organization of centrosomal microtubules, mediates delamination in the formation of the subventricular zone and regulates exit from this zone.

The subventricular zone (SVZ) in the brain is associated with gliomagenesis and resistance to treatment in glioblastoma. In this study, we investigate the prognostic role and biological characteristics of subventricular zone (SVZ) involvement in glioblastoma. We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary glioblastoma patients diagnosed between 2005-2013, and performed a multivariable Cox regression analysis to adjust the prognostic effect of SVZ involvement for clinical patient- and tumor-related factors. Protein expression patterns of a.o. markers of neural stem cellness (CD133 and GFAP-δ) and (epithelial-) mesenchymal transition (NF-κB, C/EBP-β and STAT3) were determined with immunohistochemistry on tissue microarrays containing 220 of the tumors. Molecular classification and mRNA expression-based gene set enrichment analyses, miRNA expression and SNP copy number analyses were performed on fresh frozen tissue obtained from 76 tumors. Confirmatory analyses were performed on glioblastoma TCGA/TCIA data. Involvement of the SVZ was a significant adverse prognostic factor in glioblastoma, independent of age, KPS, surgery type and postoperative treatment. Tumor volume and postoperative complications did not explain this prognostic effect. SVZ contact was associated with increased nuclear expression of the (epithelial-) mesenchymal transition markers C/EBP-β and phospho-STAT3. SVZ contact was not associated with molecular subtype, distinct gene expression patterns, or markers of stem cellness. Our main findings were confirmed in a cohort of 229 TCGA/TCIA glioblastomas. In conclusion, involvement of the SVZ is an independent prognostic factor in glioblastoma, and associates with increased expression of key markers of (epithelial-) mesenchymal transformation, but does not correlate with stem cellness, molecular subtype, or specific (mi)RNA expression patterns.

Given the importance of maximizing resection for prognosis in patients with HGG and the potential risks associated with ventricle opening, this study aimed to assess the actual increase in post-surgical complications related to lateral ventricle opening and its influence on OS and PFS. A retrospective study was conducted on newly diagnosed HGG, dividing the patients into two groups according to whether the lateral ventricle was opened (69 patients) or not opened (311 patients). PFS, OS, subependymal dissemination, distant parenchymal recurrences, the development of hydrocephalus and CSF leak were considered outcome measures. A cohort of 380 patients (154 females (40.5%) and 226 males (59.5%)) was involved in the study (median age 61 years). The PFS averaged 10.9 months (±13.3 SD), and OS averaged 16.6 months (± 16.3 SD). Among complications, subependymal dissemination was registered in 15 cases (3.9%), multifocal and multicentric progression in 56 cases (14.7%), leptomeningeal dissemination in 12 (3.2%) and hydrocephalus in 8 (2.1%). These occurrences could not be clearly justified by ventricular opening. The act of opening the lateral ventricles itself does not carry an elevated risk of dissemination, hydrocephalus or cerebrospinal fluid (CSF) leak. Therefore, if necessary, it should be pursued to achieve radical removal of the disease.