Increased variance in second electrode accuracy during deep brain stimulation and its relationship to pneumocephalus, brain shift, and clinical outcomes: A retrospective cohort study.

•Overall electrode accuracy was 0.22+/-0.4 â€‹mm with only 3 (4%) electrodes out with 2 â€‹mm from the intended target.•Accuracy was significantly worse in the GPi versus the STN and on the second side implanted.•Inaccuracy occurred in the X (lateral) plane but was not related to pneumocephalus or brain shift.

Integrins mediate a neuronal survival signal for oligodendrocytes.

Target-dependent survival of newly differentiated cells is an important part of neural development. In the case of myelin-forming oligodendrocytes, it matches the number of oligodendrocytes to the available axons [1]. In addition to growth factors, an axonal signal regulates this survival: when axons are transected, oligodendrocytes die and, conversely, when the number of axons is increased by genetic manipulation, oligodendrocyte numbers increase [2] [3]. Newly formed oligodendrocytes that fail to contact axons undergo apoptosis, and co-culture experiments that model axon-glial interactions in vitro reveal a neuronal survival effect not present in neuron-conditioned medium [4] [5], suggesting that the signal is non-diffusible and present on the surface of axons. The nature of these neuronal signals is unknown, as are the mechanisms by which they interact with growth-factor-mediated survival signals. As integrins can regulate survival in other cell types [6] [7] [8], we determined whether integrins are involved in the neuronal survival effect. We found that the laminin receptor alpha6beta1 integrin, which is expressed on oligodendrocytes, enhances the sensitivity of oligodendrocytes to the survival effect of growth factors. On the basis of this interaction between integrin and growth-factor-mediated signalling, we propose a simple model by which signals from axons and other cell types might interact to regulate oligodendrocyte cell numbers.

Expression of dominant-negative and chimeric subunits reveals an essential role for beta1 integrin during myelination.

Myelination represents a remarkable example of cell specialization and cell-cell interaction in development. During this process, axons are wrapped by concentric layers of cell membrane derived either from central nervous system (CNS) oligodendrocytes or peripheral nervous system Schwann cells. In the CNS, oligodendrocytes elaborate a membranous extension with an area of more than 1000 times that of the cell body. The mechanisms regulating this change in cell shape remain poorly understood. Signaling mechanisms regulated by cell surface adhesion receptors of the integrin family represent likely candidates. Integrins link the extracellular environment of the cell with both intracellular signaling molecules and the cytoskeleton and have been shown to regulate the activity of GTPases implicated in the control of cell shape. Our previous work has established that oligodendrocytes and their precursors express a limited repertoire of integrins. One of these, the alpha6beta1 laminin receptor, can interact with laminin-2 substrates to enhance oligodendrocyte myelin membrane formation in cell culture. However, these experiments do not address the important question of integrin function during myelination in vivo, nor do they define the respective roles of the alpha and beta subunits in the signaling pathways involved. Here, we use a dominant-negative approach to provide, for the first time, evidence that beta1 integrin function is required for myelination in vivo and use chimeric integrins to dissect apart the roles of the extracellular and cytoplasmic domains of the alpha6 subunit in the signaling pathways of myelination.

Endoscopy and implantable electronic devices.

The increasing use of implantable electronic devices such as cardiac pacemakers and neurostimulators means that they are being increasingly encountered in endoscopy departments. The electromagnetic fields generated during electrosurgery and with magnetic imaging systems have the potential to interfere with such devices. The authors present a case that highlights some of the steps necessary for minimising risk, review the evidence and summarise the currently available guidance.

Laminin-2/integrin interactions enhance myelin membrane formation by oligodendrocytes.

To examine the role of extracellular matrix (ECM)/integrin interactions in myelination we have analyzed oligodendrocyte differentiation and myelin membrane formation in oligodendrocytes grown in cell culture. We have found that the ECM substrates fibronectin, vitronectin, and laminin-2 (merosin) have no effect on differentiation, as measured by the appearance of myelin basic protein-expressing cells, but that laminin-2 substrates dramatically enhance myelin membrane formation. Blocking antibody and immunolocalization studies suggest that this effect is mediated via 1 integrins. The v integrins expressed on oligodendrocytes, in contrast, are less effective at promoting membrane formation. These results show that the interaction between laminin-2 expressed in white matter tracts and oligodendrocyte laminin-binding integrins may be an important part of the signalling mechanisms that stimulate oligodendrocytes to elaborate the extensive myelin membrane required to wrap the axon and form the myelin sheath. The results also provide a logical explanation for the abnormalities of myelination observed in humans with merosin-deficient congenital muscular dystrophy.

Mapping regions of the beta1 integrin cytoplasmic domain involved in migration and survival in primary oligodendrocyte precursors using cell-permeable homeopeptides.

The mapping of regions within integrin cytoplasmic domains responsible for the different effects on cell behaviour is an important part of an analysis of integrin-mediated signalling. In order to facilitate this analysis in primary cells, we have used cell-permeable homeopeptides to deliver sequences mimicking parts of the integrin beta1 cytoplasmic domain into the cell. In a study using oligodendrocyte precursors, the cells that give rise to myelin-forming oligodendrocytes during CNS development, we show that these peptides can be used to manipulate beta1 integrin signalling and that the regions of the cytoplasmic domain involved in migration and survival are distinct. Peptides mimicking the N-terminal portion of the cytoplasmic domain previously implicated in binding to Focal Adhesion Kinase (FAK) induce apoptosis, while peptides mimicking more C-terminal sequences do not cause cell death. In contrast they show that the NPIY sequence, the N-terminal one of two NPXY motifs previously implicated in signalling, is involved in migration. Peptides containing this sequence promote migration while alteration of NPIY to NPIA makes the peptide inhibitory to migration. Our results show that these peptides represent a novel approach to integrin signalling that allow rapid definition of critical cytoplasmic sequences in primary cells.