The interdural hematoma: A subtype of convexity subdural/dural hematoma with specific radioanatomical characteristics.

Background: Rare cases of biconvex hematomas splitting the convexity dura mater were reported and denominated interdural hematoma (IDH). Due to their rarity, little is known about their radiological characteristics, and in most cases, their invasive management with craniotomy and dural membrane excision is unnecessary. Case Description: We report here a case of single burr-hole endoscopic evacuation of an IDH and its complete resolution after the 6-month follow-up imaging. The literature review reveals 11 reported cases of IDH. Most of them are male and the mean age is 65 years (range 51-90). Most of the reported IDHs were misdiagnosed as epidural hematoma or meningioma, and therefore, they have been managed invasively through craniotomy with dural excision. Diagnosis of the interdural nature was confirmed macroscopically during surgery in all cases and histology was reported for 6 cases. Image analysis found a double dural beak sign and biconvex shape on coronal planes, subarachnoid space enlargement at the collection extremities, and irregular thick inner wall as common radiological aspects of the IDH. Conclusion: IDH is a rarely reported and often misdiagnosed dural hematoma subtype. Its invasive treatment through craniotomy is likely related to its unknown radiological characteristics. We review and raise awareness about potentially unique radiological anatomy that could avoid unnecessary invasive treatment. Moreover, we report the first case of endoscopically evacuated IDH with long-term follow-up imaging showing complete resolution.

Transplanted Embryonic Neurons Improve Functional Recovery by Increasing Activity in Injured Cortical Circuits.

Transplantation of appropriate neuronal precursors after injury is a promising strategy to reconstruct cortical circuits, but the efficiency of these approaches remains limited. Here, we applied targeted apoptosis to selectively ablate layer II/III pyramidal neurons in the rat juvenile cerebral cortex and attempted to replace lost neurons with their appropriate embryonic precursors by transplantation. We demonstrate that grafted precursors do not migrate to replace lost neurons but form vascularized clusters establishing reciprocal synaptic contacts with host networks and show functional integration. These heterotopic neuronal clusters significantly enhance the activity of the host circuits without causing epileptic seizures and attenuate the apoptotic injury-induced functional deficits in electrophysiological and behavioral tests. Chemogenetic activation of grafted neurons further improved functional recovery, and the persistence of the graft was necessary for maintaining restored functions in adult animals. Thus, implanting neuronal precursors capable to form synaptically integrated neuronal clusters combined with activation-based approaches represents a useful strategy for helping long-term functional recovery following brain injury.

Transient Deregulation of Canonical Wnt Signaling in Developing Pyramidal Neurons Leads to Dendritic Defects and Impaired Behavior.

During development, the precise implementation of molecular programs is a key determinant of proper dendritic development. Here, we demonstrate that canonical Wnt signaling is active in dendritic bundle-forming layer II pyramidal neurons of the rat retrosplenial cortex during dendritic branching and spine formation. Transient downregulation of canonical Wnt transcriptional activity during the early postnatal period irreversibly reduces dendritic arbor architecture, leading to long-lasting deficits in spatial exploration and/or navigation and spatial memory in the adult. During the late phase of dendritogenesis, canonical Wnt-dependent transcription regulates spine formation and maturation. We identify neurotrophin-3 as canonical Wnt target gene in regulating dendritogenesis. Our findings demonstrate how temporary imbalance in canonical Wnt signaling during specific time windows can result in irreversible dendritic defects, leading to abnormal behavior in the adult.

Electrophysiological Evidence for the Development of a Self-Sustained Large-Scale Epileptic Network in the Kainate Mouse Model of Temporal Lobe Epilepsy.

Most research on focal epilepsy focuses on mechanisms of seizure generation in the primary epileptic focus (EF). However, neurological deficits that are not directly linked to seizure activity and that may persist after focus removal are frequent. The recruitment of remote brain regions of an epileptic network (EN) is recognized as a possible cause, but a profound lack of experimental evidence exists concerning their recruitment and the type of pathological activities they exhibit. We studied the development of epileptic activities at the large-scale in male mice of the kainate model of unilateral temporal lobe epilepsy using high-density surface EEG and multiple-site intracortical recordings. We show that, along with focal spikes and fast ripples that remain localized to the injected hippocampus (i.e., the EF), a subpopulation of spikes that propagate across the brain progressively emerges even before the expression of seizures. The spatiotemporal propagation of these generalized spikes (GSs) is highly stable within and across animals, defining a large-scale EN comprising both hippocampal regions and frontal cortices. Interestingly, GSs are often concomitant with muscular twitches. In addition, while fast ripples are, as expected, highly frequent in the EF, they also emerge in remote cortical regions and in particular in frontal regions where GSs propagate. Finally, we demonstrate that these remote interictal activities are dependent on the focus in the early phase of the disease but continue to be expressed after focus silencing at later stages. Our results provide evidence that neuronal networks outside the initial focus are progressively altered during epileptogenesis.SIGNIFICANCE STATEMENT It has long been held that the epileptic focus is responsible for triggering seizures and driving interictal activities. However, focal epilepsies are associated with heterogeneous symptoms, calling into question the concept of a strictly focal disease. Using the mouse model of hippocampal sclerosis, this work demonstrates that focal epilepsy leads to the development of pathological activities specific to the epileptic condition, notably fast ripples, that appear outside of the primary epileptic focus. Whereas these activities are dependent on the focus early in the disease, focus silencing fails to control them in the chronic stage. Thus, dynamical changes specific to the epileptic condition are built up outside of the epileptic focus along with disease progression, which provides supporting evidence for network alterations in focal epilepsy.

Astrocytes spatially restrict VEGF signaling by polarized secretion and incorporation of VEGF into the actively assembling extracellular matrix.

The spatial organization of vascular endothelial growth factor (VEGF) signaling is a key determinant of vascular patterning during development and tissue repair. How VEGF signaling becomes spatially restricted and the role of VEGF secreting astrocytes in this process remains poorly understood. Using a VEGF-GFP fusion protein and confocal time-lapse microscopy, we observed the intracellular routing, secretion and immobilization of VEGF in scratch-activated living astrocytes. We found VEGF to be directly transported to cell-extracellular matrix attachments where it is incorporated into fibronectin fibrils. VEGF accumulated at ß1 integrin containing fibrillar adhesions and was translocated along the cell surface prior to internalization and degradation. We also found that only the astrocyte-derived, matrix-bound, and not soluble VEGF decreases ß1 integrin turnover in fibrillar adhesions. We suggest that polarized VEGF release and ECM remodeling by VEGF secreting cells is key to control the local concentration and signaling of VEGF. Our findings highlight the importance of astrocytes in directing VEGF functions and identify these mechanisms as promising target for angiogenic approaches.

Ivy sign, misery perfusion, and asymptomatic moyamoya disease: FLAIR imaging and (15)O-gas positron emission tomography.

BACKGROUND: The prevalence of ivy sign on fluid-attenuated inversion recovery (FLAIR) imaging in patients with asymptomatic moyamoya disease is unclear. The aim of this study was to clarify the incidence of ivy sign in these patients, as well as the correlation between MRI and (15)O gas PET findings. METHODS: A retrospective analysis including 16 consecutive patients with asymptomatic moyamoya disease enrolled between 2001 and 2010 in a single center. FLAIR imaging at the initial visit was categorized as ivy sign present, negative, or equivocal. Hemodynamic and metabolic parameters were quantified in 11 of 16 patients by (15)O-gas positron emission tomography, and the relationship between ivy sign and (15)O-gas PET parameters was analyzed. Cerebrovascular events within the follow-up period (54 ± 28 months) were also examined. RESULTS: Five of 16 asymptomatic moyamoya patients (31.3 %) had positive ivy sign (6/30 hemispheres, 20 %). In (15)O-gas PET examinations, 18 % of 22 hemispheres had elevated oxygen extraction fraction values that were significantly associated with positive ivy sign. Of these 16 asymptomatic moyamoya patients, six patients (37.5 %) underwent combined surgical revascularization. In this series, no patients experienced ischemic stroke, but one had intraventricular bleeding 1 year after surgery. CONCLUSIONS: Ivy sign on FLAIR imaging is still not rare in patients with moyamoya disease, even when asymptomatic. Although optimal management is still under debate, ivy sign may be an indicator of misery perfusion, and patients with asymptomatic moyamoya disease and ivy sign on FLAIR imaging will benefit from more careful follow-up.

Polysialic acid-neural cell adhesion molecule in brain plasticity: from synapses to integration of new neurons.

Isoforms of the neuronal cell adhesion molecule (NCAM) carrying the linear homopolymer of alpha 2,8-linked sialic acid (polysialic acid, PSA) have emerged as particularly attractive candidates for promoting plasticity in the nervous system. The large negatively charged PSA chain of NCAM is postulated to be a spacer that reduces adhesion forces between cells allowing dynamic changes in membrane contacts. Accumulating evidence also suggests that PSA-NCAM-mediated interactions lead to activation of intracellular signaling cascades that are fundamental to the biological functions of the molecule. An important role of PSA-NCAM appears to be during development, when its expression level is high and where it contributes to the regulation of cell shape, growth or migration. However, PSA-NCAM does persist in adult brain structures such as the hippocampus that display a high degree of plasticity where it is involved in activity-induced synaptic plasticity. Recent advances in the field of PSA-NCAM research have not only consolidated the importance of this molecule in plasticity processes but also suggest a role for PSA-NCAM in the regulation of higher cognitive functions and psychiatric disorders. In this review, we discuss the role and mode of actions of PSA-NCAM in structural plasticity as well as its potential link to cognitive processes.

Effects of ketamine on the developing central nervous system.

Ketamine is a widely used drug in pediatric anesthesia practice, acting primarily through the blockade of the N-methyl-D-aspartate (NMDA) type of glutamate receptors. A growing body of laboratory evidence, accumulated during the past few years, suggests that this drug could have potential adverse effects on the developing central nervous system. The goal of this short review is to give a brief synopsis of experimental work indicating ketamine-induced developmental neurotoxicity as well as to discuss potential limitations concerning extrapolation of these studies to clinical practice.

PSA-NCAM in postnatally generated immature neurons of the olfactory bulb: a crucial role in regulating p75 expression and cell survival.

In the mammalian brain, ongoing neurogenesis via the rostral migratory stream (RMS) maintains neuronal replacement in the olfactory bulb throughout life. Mechanisms that regulate the final number of new neurons in this system include proliferation, migration and apoptosis. Here we show that the polysialylated isoforms of the neural cell adhesion molecule (PSA-NCAM) act as a pro-survival molecule in immature newborn neurons. Confocal microscopic analysis revealed a threefold increase in TUNEL-positive cells in the subventricular zone (SVZ) and the RMS of transgenic animals lacking the gene encoding NCAM (NCAM(-/-)), as compared with wild types. The enhanced apoptotic cell death occurred specifically in the population of mCD24-positive newborn neurons, but not in GFAP-positive astrocytes. Using in vitro cultures of purified SVZ-derived neurons, we demonstrate that the loss or inactivation of PSA on NCAM, as well as the deletion of NCAM, lead to reduced survival in response to neurotrophins including BDNF and NGF. These changes in cell survival are accompanied by an upregulation of p75 neurotrophin receptor expression in vitro as well as in vivo. Furthermore, the negative effects of PSA-NCAM inactivation on cell survival could be prevented by the pharmacological blockade of the p75 receptor-signaling pathway. We propose that PSA-NCAM may promote survival by controlling the expression of the p75 receptor in developing neurons.

The polysialylated neural cell adhesion molecule promotes neurogenesis in vitro.

A characteristic feature of neurogenic sites in the postnatal brain is the expression of the polysialylated forms of the neural cell adhesion molecule (PSA-NCAM). To investigate the role of PSA-NCAM in generation of neuronal populations, we developed an in vitro model where neurogenesis occurs in primary cortical cultures following serum withdrawal. We show that removal or inactivation of the PSA tail of NCAM in these cultures leads to a significant decrease in the number of newly generated neurons. Similarly, cultures prepared from NCAM knock-out mice exhibit a significantly reduced neurogenesis. Pulse-chase experiments using the proliferation marker BrdU reveal that the lack of PSA does not affect the mitotic rate of neural progenitors but rather, it reduces the early survival of newly generated neurons. These results suggest that, in addition to its role in the migration of neuronal progenitors, PSA-NCAM is required for the adequate survival of these cells.

Clinically relevant concentrations of propofol but not midazolam alter in vitro dendritic development of isolated gamma-aminobutyric acid-positive interneurons.

BACKGROUND: Recent laboratory studies showed that exposure to supraclinical concentrations of propofol can induce cell death of immature neurons. However, no data are available regarding the effects of clinically relevant concentrations of this agent on neuronal development. The authors addressed this issue by evaluating the effect of propofol on dendritic growth and arbor expansion of developing gamma-aminobutyric acid-positive (GABAergic) interneurons. METHODS: Immature neuroblasts were isolated from the newborn rat subventricular zone and differentiated into GABAergic interneurons in culture. In addition to cell death, the effects of increasing concentrations and durations of propofol exposure on neuronal dendritic development were evaluated using the following morphologic parameters: total dendritic length, primary dendrites, branching point, and Scholl analysis. RESULTS: The authors demonstrate that propofol induced cell death of GABAergic neurons at concentrations of 50 microg/ml or greater. As little as 1 microg/ml propofol significantly altered several aspects of dendritic development, and as little as 4 h of exposure to this agent resulted in a persistent decrease in dendritic growth. In contrast, application of midazolam did not affect neuronal development. CONCLUSION: Short-term exposure of immature developing GABAergic neurons to clinically relevant concentrations of propofol can induce long-term changes in dendritic arbor development. These results suggest that propofol anesthesia during central nervous system development could interfere with the molecular mechanisms driving the differentiation of GABAergic neurons and thus could potentially lead to impairment of neural networks.