Walls Of Lateral Ventricles Research Articles

Strain and dyssynchrony in fetuses with congenital heart disease compared to normal controls using speckle tracking echocardiography (STE).

Objective To compare myocardial strain and mechanical dyssynchrony in fetuses with congenital heart disease (CHD) to normal controls using speckle tracking echocardiography (STE). Methods In this comparative cross-sectional study 23 fetuses with CHD and 105 normal controls between 19 and 41 weeks of gestation were assessed with STE. The STE sample box was placed over the myocardium of both ventricles. The parameters of interest included the segmental strain of the left (LV-S) and right lateral ventricle wall (RV-S) and the global ventricular strain of both chambers (2C-S). In order to separately assess the LV, we placed the STE sample box over the myocardium of the LV. We calculated the strain of the LV lateral wall (LW-S), the septum (SEPT-S) and the global ventricular strain of the single LV (1C-S). Furthermore, we analyzed the differences in timing of negative peak myocardial strain between the LV and RV (two-chamber dyssynchrony, 2C-DYS) and also within the LV between the lateral wall and the septum (one-chamber dyssynchrony, 1C-DYS). Results The evaluation of strain and mechanical dyssynchrony was feasible in all cases. Compared to normal controls, fetuses with CHD showed lower segmental and global strain values and the extent of 2C-DYS and 1C-DYS was higher than in the healthy control group. Conclusion The deterioration of myocardial function in CHD can be measured with STE. The assessment of strain and dyssynchrony with STE may be useful for distinguishing fetuses with CHD from healthy fetuses.

Knockdown of circulating C1 inhibitor induces neurovascular impairment, glial cell activation, neuroinflammation, and behavioral deficits.

The cross-talk between blood proteins, immune cells, and brain function involves complex mechanisms. Plasma protein C1 inhibitor (C1INH) is an inhibitor of vascular inflammation that is induced by activation of the kallikrein-kinin system (KKS) and the complement system. Knockout of C1INH was previously correlated with peripheral vascular permeability via the bradykinin pathway, yet there was no evidence of its correlation with blood-brain barrier (BBB) integrity and brain function. In order to understand the effect of plasma C1INH on brain pathology via the vascular system, we knocked down circulating C1INH in wild-type (WT) mice using an antisense oligonucleotide (ASO), without affecting C1INH expression in peripheral immune cells or the brain, and examined brain pathology. Long-term elimination of endogenous C1INH in the plasma induced the activation of the KKS and peritoneal macrophages but did not activate the complement system. Bradykinin pathway proteins were elevated in the periphery and the brain, resulting in hypotension. BBB permeability, extravasation of plasma proteins into the brain parenchyma, activation of glial cells, and elevation of pro-inflammatory response mediators were detected. Furthermore, infiltrating innate immune cells were observed entering the brain through the lateral ventricle walls and the neurovascular unit. Mice showed normal locomotion function, yet cognition was impaired and depressive-like behavior was evident. In conclusion, our results highlight the important role of regulated plasma C1INH as it acts as a gatekeeper to the brain via the neurovascular system. Thus, manipulation of C1INH in neurovascular disorders might be therapeutically beneficial.

Transgenic increase in the β-endorphin concentration in cerebrospinal fluid alleviates morphine-primed relapse behavior through the μ opioid receptor in rats.

BackgroundOpioid‐primed relapse is a global burden. Although current strategies have improved, optimal therapy is urgently needed.MethodsA recombinant adenovirus (Ad‐NEP) expressing β‐endorphin (β‐EP) was designed and injected intracerebroventricularly (icv) into the right lateral ventricle in rats. Spatial and temporal β‐EP expression in the lateral ventricle wall, subventricular zone and adjacent choroid plexus and the β‐EP concentration in the cerebrospinal fluid (CSF) were observed during a 21‐day period. A morphine priming‐induced conditioned place preference (CPP) rat model was established. The β‐EP‐ir neuron counts, CSF β‐EP concentration, and CPP score, which were used to evaluate morphine‐primed reinstatement following extinction, were recorded 7 days after the icv injection. Additionally, the rats were pretreated with the irreversible μ opioid receptor antagonist β‐funaltrexamine (β‐FNA) and the selective κ opioid receptor antagonist nor‐binaltorphimine (nor‐BNI) to identify the receptor‐dependent mechanism.ResultsBoth peak β‐EP expression in target neurons and the peak CSF β‐EP concentration occurred 7 to 8 days after Ad‐NEP icv injection. The sustainable increase in the CSF β‐EP concentration was correlated with a decrease in the CPP score 7 days after the Ad‐NEP icv injection. Furthermore, reinstatement was almost reversed by β‐FNA pretreatment 24 hours before the behavioral test, but nor‐BNI had little effect.ConclusionThe increasing cerebrospinal fluid β‐endorphin concentrations showed that the therapeutic effect on opioid relapse occurred predominantly through a μ opioid receptor‐dependent mechanism. The Ad‐NEP adenovirus can be considered an alternative therapy for opioid relapse.

Relationship between the location of the ventricular catheter tip and the ventriculoperitoneal shunt malfunction

ObjectiveVentriculoperitoneal (VP) shunt is the most common neurosurgical procedure to treat obstructive and communicating hydrocephalus, but failures are frequent. The most common causes of shunt failure are malpositioning and obstruction of the ventricular catheter by debris or blood clothes. The knowledge of the relationship between ventricular catheter tip position, etiology of hydrocephalus and patient’s age with shunt malfunction may be useful to avoid shunt failure. Patients and MethodsWe retrospectively analyze 89 adult patients affected by obstructive and communicating hydrocephalus operated with Ventriculoperitoneal shunt at our Institute. Patients with evident abdominal shunt malfunction were excluded from this study. Statistical analysis was performed in the group of patients with intracranial catheter malfunction in order to correlate shunt malfunction with the position of the catheter tip in brain ventricles, etiology of hydrocephalus and patient’s age. ResultsShunt revision was performed in 26 patients out of 89 and cranial catheter malfunction was documented in 11 patients out of 26. Tip position in Monro foramen, lateral ventricles and third ventricle (“good position”) had a lower rate of surgical shunt revision compared to septum pellucidum and wall of lateral ventricle (“bad position”) p value = 0,049. No statistical significant association was observed between shunt malfunction and etiology of the hydrocephalus or patient’s age. ConclusionsVentricular catheter tip position is one the most important factor for shunt function.

Carotid artery stenting for patients with occipital-vertebral anastomosis.

We report the outcomes of carotid artery stenting for patients with angiographically visible occipital artery-vertebral artery anastomosis. Among 47 consecutive patients who underwent carotid artery stenting from January 2007 to December 2010, seven patients for whom cerebral angiograms clearly showed occipital artery-vertebral artery anastomosis were selected. Four different protection methods were used: distal internal carotid artery protection; carotid flow reversal; seatbelt and airbag technique; and double protection method of protecting both the external and internal carotid artery. One patient with distal internal carotid artery protection showed a high-intensity lesion at the border of the upper thalamus, internal capsule and lateral ventricle wall after carotid artery stenting. The other patient with the double protection method did not show any high-intensity lesions on postoperative diffusion-weighted imaging in the vertebrobasilar territory. All seven patients with visible occipital artery-vertebral artery anastomosis showed ipsilateral vertebral artery severe stenosis or occlusion. Large occipital artery-vertebral artery anastomosis may be a pathway for embolic materials during carotid artery stenting. External carotid artery protection is recommended for carotid artery stenting in such patients.

Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus.

Adult neurogenesis takes place in the brain subventricular zone (SVZ) in the lateral walls of lateral ventricles and subgranular zone (SGZ) in the hippocampal dentate gyrus (HDG), and functions to supply newborn neurons for normal brain functionality. Subchronic Mn exposure is known to disrupt adult neurogenesis in the SVZ. This study was designed to determine whether Mn exposure disturbed neurogenesis within the adult HDG. Adult rats (10 weeks old) received a single dose of bromodeoxyuridine (BrdU) at the end of 4-week Mn exposure to label the proliferating cells. Immunostaining and cell counting data showed that BrdU(+) cells in Mn-exposed HDG were about 37% lower than that in the control (p < .05). The majority of BrdU(+) cells were identified as Sox2(+) cells. Another set of adult rats received BrdU injections for 3 consecutive days followed by 2- or 4-week Mn exposure to trace the fate of BrdU-labeled cells in the HDG. The time course studies indicated that Mn exposure significantly reduced the survival rate (54% at 2 weeks and 33% at 4 weeks), as compared with that in the control (80% at 2 weeks and 51% at 4 weeks) (p < .01). A significant time-dependent migration of newborn cells from the SGZ toward the granule cell layer was also observed in both control and Mn-exposed HDG. Triple-stained neuroblasts and mature neurons further revealed that Mn exposure significantly inhibited the differentiation of immature neuroblasts into mature neurons in the HDG. Taken together, these observations suggest that subchronic Mn exposure results in a reduced cell proliferation, diminished survival of adult-born neurons, and inhibited overall neurogenesis in the adult HDG. Impaired adult neurogenesis is likely one of the mechanisms contribute to Mn-induced Parkinsonian disorder.

Ultrasound-guided placement of ventricular catheters in first-time pediatric VP shunt surgery.

Ventriculo-peritoneal (VP) shunts are effective for treatment of hydrocephalus in all age groups; however, they are associated with complications, a common one being ventricular catheter (VC) obstruction. VC position is likely to influence VC survival; however, most VCs are positioned freehand without guidance. This paper describes the accuracy of ultrasound guidance for VC placement and the impact of tip location on VC occlusion rate. This is a retrospective cohort study of hydrocephalic children with first-time VP shunt and ultrasound-guided VC placement. Data recorded were age, sex, cause of hydrocephalus, side (left or right) and location (frontal or occipital) of VC, and exact postoperative position within the ventricle on first postoperative imaging: middle of ventricle (optimal position), near or touching the medial or lateral ventricle wall, within the third ventricle, and at the contralateral side. Of the 128 screened patients, 85 had a first postoperative imaging that clearly defined the VC position and were included. The follow-up was at least 12months. Seventy-three percent of VCs were placed on the right and 71% via a frontal burhole. Eighty-three of 85 VC tips (95%) were in the intended ventricle, 61% at optimal position. Nine of 85 VCs (10%) obstructed within the first 12months. Seven of nine (78%) obstructed VCs were located in a nonoptimal position (p = 0.016). Two of nine (22%) obstructed VCs entered through a frontal and seven of nine (78%) through an occipital burrhole (p = 0.016). Ultrasound-guided VC placement is as precise as frameless navigated placement. The optimal VC position was associated to a significant lower VC obstruction rate. The frontal position was superior to the occipital. Intraoperative US guidance is fast with almost no extra time and no extra cost. US-guided VC placement should become standard of care in VP shunt surgery.

Parvalbumin-expressing ependymal cells in rostral lateral ventricle wall adhesions contribute to aging-related ventricle stenosis in mice.

Aging-associated ependymal-cell pathologies can manifest as ventricular gliosis, ventricle enlargement, or ventricle stenosis. Ventricle stenosis and fusion of the lateral ventricle (LV) walls is associated with a massive decline of the proliferative capacities of the stem cell niche in the affected subventricular zone (SVZ) in aging mice. We examined the brains of adult C57BL/6 mice and found that ependymal cells located in the adhesions of the medial and lateral walls of the rostral LVs upregulated parvalbumin (PV) and displayed reactive phenotype, similarly to injury-reactive ependymal cells. However, PV+ ependymal cells in the LV-wall adhesions, unlike injury-reactive ones, did not express glial fibrillary acidic protein. S100B+/PV+ ependymal cells found in younger mice diminished in the LV-wall adhesions throughout aging. We found that periventricular PV-immunofluorescence showed positive correlation to the grade of LV stenosis in nonaged mice (<10-month-old), and that the extent of LV-wall adhesions and LV stenosis was significantly lower in mid-aged (>10-month-old) PV-knock out (PV-KO) mice. This suggests an involvement of PV+ ependymal cells in aging-associated ventricle stenosis. Additionally, we observed a time-shift in microglial activation in the LV-wall adhesions between age-grouped PV-KO and wild-type mice, suggesting a delay in microglial activation when PV is absent from ependymal cells. Our findings implicate that compromised ependymal cells of the adhering ependymal layers upregulate PV and display phenotype shift to "reactive" ependymal cells in aging-related ventricle stenosis; moreover, they also contribute to the progression of LV-wall fusion associated with a decline of the affected SVZ-stem cell niche in aged mice.

Central Nervous System and Vertebrae Development in Horses: a Chronological Study with Differential Temporal Expression of Nestin and GFAP.

The neural system is one of the earliest systems to develop and the last to be fully developed after birth. This study presents a detailed description of organogenesis of the central nervous system (CNS) at equine embryonic/fetal development between 19 and 115days of pregnancy. The expression of two important biomarkers in the main structure of the nervous system responsible for neurogenesis in the adult individual, and in the choroid plexus, was demonstrated by Nestin and glial fibrillary acid protein (GFAP) co-labeling. In the 29th day of pregnancy in the undifferentiated lateral ventricle wall, the presence of many cells expressing Nestin and few expressing GFAP was observed. After the differentiation of the lateral ventricle wall zones at 60days of pregnancy, the subventricular zone, which initially had greater number of Nestin+ cells, began to show higher numbers of GFAP+ cells at 90days of pregnancy. A similar pattern was observed for Nestin+ and GFAP+ cells during development of the choroid plexus. This study demonstrates, for the first time, detailed chronological aspects of the equine central nervous system organogenesis associated with downregulation of Nestin and upregulation of GFAP expression.

Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain.

In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc.

Analysis of tuberous sclerosis initially manifested as hypomelanotic macules in 12 infants

Objective To investigate clinical characteristics of tuberous sclerosis (TSC) without nervous system abnormalities in infants. Methods Clinical manifestations of 12 infants with TSC were analyzed. Reflectance confocal microscopy (RCM) was performed in 5 of the 12 infants. Two patients underwent histopathological examination and electron microscopic examination. Results The age at first clinic visit for TSC ranged from 2 to 18 months (median, 8.6 months) among these patients. Before occurrence of nervous symptom, TSC mainly manifested as hypomelanotic macules, nodules in the subependymal layer or walls of lateral ventricles of the brain, cardiac rhabdomyoma and multiple renal cysts. RCM revealed intact dermal papillary rings with low reflectivity and obscure boundaries in 5 infants. Histopathological examination showed a local decrease in melanocytes and pigment granules in basal cells. Electron microscopic examination showed a normal number of melanin granules in the cytoplasm of melanocytes in the basal layer. Conclusions Before appearance of nervous system abnormalities, TSC mainly manifests as hypomelanotic macules in infants, and is easily confused with vitiligo in clinic. RCM examination may serve as a useful method to distinguish infant TSC from hypopigmented diseases. Key words: Tuberous sclerosis; Infant; Hypopigmentation; Vitiligo; Microscopy, confocal

RTRB-17NEURAL PROGENITOR CELL (NPC) SPARING RADIATION THERAPY PLUS TEMOZOLOMIDE IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) ASSOCIATED WITH COGNITIVE FUNCTION BUT NOT TUMOR OUTCOMES: RESULTS OF A SINGLE ARM PROSPECTIVE CLINICAL TRIAL

BACKGROUND: NPC may be associated with neuro-cognitive sequelae of RT, but may contribute to GBM recurrence. This prospective trial limited RT dose to NPC niches to evaluate the impact on neuro-cognitive function, tumor recurrence, and survival in newly diagnosed GBM. METHODS: 30 adults with newly diagnosed GBM and KPS > 60 enrolled. Each received 60 Gy in 30 fractions with concurrent/adjuvant temozolomide. Standard planning target volumes (PTV) delineated. Subventricular zone (SVZ, 0.5 cm adjacent to lateral wall of lateral ventricle) and hippocampus (expanded 5 mm) defined as NPC niches. IMRT limited RT dose to NPC niches without compromising PTV dose. Tests of global cognitive function, processing speed, verbal learning/memory, and executive function obtained at baseline, 6, 12, 24 months. OS/PFS estimated using Kaplan-Meier method. Cox regression model evaluated relationships between performance on cognitive testing, radiation doses to NPC regions, survival outcomes. RESULTS: 16 men, 14 women; 17 gross total resection, 13 subtotal resection; 8 MGMT methylated, 11 unmethylated, 10 unknown; 6 multifocal. Median OS: 15.9 months (95% CI 12.6-35.4). Median PFS: 7.3 months (95% CI 4.8-9.3 months). Mean dose to ipsilateral and contralateral hippocampus: 43.8 Gy (range 9.0 - 61.4) and 17.3 Gy (range 1.7 - 40.2), respectively. Mean dose to ipsilateral and contralateral SVZ: 38.9 Gy (range 6 - 56.2) and 20.5 Gy (range 4.4 - 48.0), respectively. At a minimum FU of 13 months, 2 patients recurred in spared NPC volume. Higher mean RT dose to bilateral SVZ was associated with greater deterioration in performance between baseline and 6 /12 months on processing speed (Coding, p = 0.03). No relationship between RT dose to NPC niches and PFS, OS, or recurrence patterns. CONCLUSIONS: This prospective trial suggests a relationship between RT dose to NPC niches and neuro-psychological function in newly diagnosed GBM without a detrimental effect on recurrence or survival outcomes.

Embryonic Nkx2.1-expressing neural precursor cells contribute to the regional heterogeneity of adult V–SVZ neural stem cells

The adult ventricular–subventricular zone (V–SVZ) of the lateral ventricle produces several subtypes of olfactory bulb (OB) interneurons throughout life. Neural stem cells (NSCs) within this zone are heterogeneous, with NSCs located in different regions of the lateral ventricle wall generating distinct OB interneuron subtypes. The regional expression of specific transcription factors appears to correspond to such geographical differences in the developmental potential of V–SVZ NSCs. However, the transcriptional definition and developmental origin of V–SVZ NSC regional identity are not well understood. In this study, we found that a population of NSCs in the ventral region of the V–SVZ expresses the transcription factor Nkx2.1 and is derived from Nkx2.1-expressing (Nkx2.1+) embryonic precursors. To follow the fate of Nkx2.1+ cells and their progeny in vivo, we used mice with an Nkx2.1-CreER “knock-in” allele. Nkx2.1+ V–SVZ NSCs labeled in adult mice generated interneurons for the deep granule cell layer of the OB. Embryonic brain Nkx2.1+ precursors labeled at embryonic day 12.5 gave rise to Nkx2.1+ NSCs of the ventral V–SVZ in postnatal and adult mice. Thus, embryonic Nkx2.1+ neural precursors give rise to a population of Nkx2.1+ NSCs in the ventral V–SVZ where they contribute to the regional heterogeneity of V–SVZ NSCs.

3D Modeling of the Lateral Ventricles and Histological Characterization of Periventricular Tissue in Humans and Mouse.

The ventricular system carries and circulates cerebral spinal fluid (CSF) and facilitates clearance of solutes and toxins from the brain. The functional units of the ventricles are ciliated epithelial cells termed ependymal cells, which line the ventricles and through ciliary action are capable of generating laminar flow of CSF at the ventricle surface. This monolayer of ependymal cells also provides barrier and filtration functions that promote exchange between brain interstitial fluids (ISF) and circulating CSF. Biochemical changes in the brain are thereby reflected in the composition of the CSF and destruction of the ependyma can disrupt the delicate balance of CSF and ISF exchange. In humans there is a strong correlation between lateral ventricle expansion and aging. Age-associated ventriculomegaly can occur even in the absence of dementia or obstruction of CSF flow. The exact cause and progression of ventriculomegaly is often unknown; however, enlarged ventricles can show regional and, often, extensive loss of ependymal cell coverage with ventricle surface astrogliosis and associated periventricular edema replacing the functional ependymal cell monolayer. Using MRI scans together with postmortem human brain tissue, we describe how to prepare, image and compile 3D renderings of lateral ventricle volumes, calculate lateral ventricle volumes, and characterize periventricular tissue through immunohistochemical analysis of en face lateral ventricle wall tissue preparations. Corresponding analyses of mouse brain tissue are also presented supporting the use of mouse models as a means to evaluate changes to the lateral ventricles and periventricular tissue found in human aging and disease. Together, these protocols allow investigations into the cause and effect of ventriculomegaly and highlight techniques to study ventricular system health and its important barrier and filtration functions within the brain.

Ependymal cell differentiation, from monociliated to multiciliated cells.

Primary and motile cilia differ in their structure, composition, and function. In the brain, primary cilia are immotile signalling organelles present on neural stem cells and neurons. Multiple motile cilia are found on the surface of ependymal cells in all brain ventricles, where they contribute to the flow of cerebrospinal fluid. During development, monociliated ependymal progenitor cells differentiate into multiciliated ependymal cells, thus providing a simple system for studying the transition between these two stages. In this chapter, we provide protocols for immunofluorescence staining of developing ependymal cells in vivo, on whole mounts of lateral ventricle walls, and in vitro, on cultured ependymal cells. We also provide a list of markers we currently use to stain both types of cilia, including proteins at the ciliary membrane and tubulin posttranslational modifications of the axoneme.

Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse.

The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction.

De novo expression of parvalbumin in ependymal cells in response to brain injury promotes ependymal remodeling and wound repair.

The calcium-binding protein parvalbumin (PV) hallmarks subpopulations of interneurons in the murine brain. We serendipitously observed the de novo expression of PV in ependymal cells of the lateral ventricle wall following in vivo lesioning and brain slicing for the preparation of organotypic hippocampal slice cultures (OHSCs). In OHSCs, de novo PV-expression begins shortly after the onset of culturing, and the number of ependymal cells implicated in this process increases with time. PV-immunopositive ependymal cells aggregate and form compact cell clusters, which are characterized by lumen-formation and beating cilia. Scratches inflicted on such clusters with a sharp knife are rapidly closed. Exposure of OHSCs to NF-КB-inhibitors and to antioxidants reduces PV-expression in ependymal cells, thereby implicating injury-induced inflammation in this process. Indeed, in vivo stab injury enhances PV-expression in ependymal cells adjacent to the lesion, whereas neuraminidase denudation is without effect. PV-knock-out mice manifest an impaired wound-healing response to in vivo injury, and a reduced scratch-wound reparation capacity in OHSCs. Whole-transcriptome analysis of ependymal-cell clusters in OHSCs revealed down-regulation of genes involved in cytoskeletal rearrangement, cell motility and cell adhesion in PV-knock out mice as compared with wild-type mice. Our data indicate that the injury-triggered up-regulation of PV-expression is mediated by inflammatory cytokines, and promotes the motility and adhesion of ependymal cells, thereby contributing to leakage closure by the re-establishment of a continuous ependymal layer.

Neurons' New Birthday

Neuroscience Mice generate new olfactory neurons throughout adult life. Although humans seem not to generate new olfactory neurons in adulthood, the site at which those new neurons are born, the lateral ventricle wall, seems to generate neurons in both mice and humans. Ernst et al. use carbon-14 dating from nuclear bomb test exposures to compare the birth dates of neurons to the birth dates of the people being analyzed. The results show that unexpectedly, some striatal neurons are generated after birth. Calculations indicate that neurogenesis from the lateral ventricle wall in the adult human supplies interneurons in the striatum. Cell 156 , 1072 (2014).

Neurogenesis in the Striatum of the Adult Human Brain

In most mammals, neurons are added throughout life in the hippocampus and olfactory bulb. One area where neuroblasts that give rise to adult-born neurons are generated is the lateral ventricle wall of the brain. We show, using histological and carbon-14 dating approaches, that in adult humans new neurons integrate in the striatum, which is adjacent to this neurogenic niche. The neuronal turnover in the striatum appears restricted to interneurons, and postnatally generated striatal neurons are preferentially depleted in patients with Huntington's disease. Our findings demonstrate a unique pattern of neurogenesis in the adult human brain.

Axons take a dive: Specialized contacts of serotonergic axons with cells in the walls of the lateral ventricles in mice and humans.

In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular-subventricular zone (V-SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells.