Thinking Ahead on Deep Brain Stimulation: An Analysis of the Ethical Implications of a Developing Technology.

Deep brain stimulation (DBS) is a developing technology. New generations of DBS technology are already in the pipeline, yet this particular fact has been largely ignored among ethicists interested in DBS. Focusing only on ethical concerns raised by the current DBS technology is, albeit necessary, not sufficient.

Expression of activating transcription factor 3 (ATF 3) and caspase 3 in Schwann cells and axonal outgrowth after sciatic nerve repair in diabetic BB rats.

The aim of this study was to evaluate nerve regeneration in relation to the transcription factor, Activating Transcription Factor 3 (ATF 3), and an apoptotic marker, caspase 3, in the Schwann cells of diabetic BB rats (i.e. display type 1 diabetes phenotype).

Nanomodified surfaces and neurite outgrowth.

Here we describe our attempts to study the interaction of nanomodified surfaces with neurons and macrophages. Surfaces with nano-sized topographies produced by UV lithography, electrochemical etching, nanoimprint lithography, microdispensing, or by electrospinning of plastic nanofibers or by making plastic replicas of the extracellular matrix with nanoresolution were found to guide neurite outgrowth extending from the dorsal root and the superior cervical ganglion in tissue culture. Ordered arrays of nanowires acted as particularly potent guides for the neurites.

Regeneration in, and properties of, extracted peripheral nerve allografts and xenografts.

When not enough conventional autologous nerve grafts are available, alternatives are needed to bridge nerve defects. Our aim was to study regeneration of nerves in chemically-extracted acellular nerve grafts from frogs, mice, humans (fresh and stored sural nerve), pigs and rats when defects in rat sciatic nerves were bridged. Secondly, we compared two different extraction procedures (techniques described by Sondell et al.

Polystyrene replicas of neuronal basal lamina act as excellent guides for regenerating neurites.

Various scaffolds, natural or artificial, have been used for neural repair, including basal lamina scaffolds obtained through extraction of nerves. Here we tested whether plastic casts of such preparations could be used for neurite guidance. To this end, longitudinal micron thick sections of rat sciatic nerve were extracted with detergents and treated with Dnase, yielding an acellular basal lamina master.

Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats.

Background: Extracellular-signal regulated kinase (ERK1/2) is activated by nerve damage and its activation precedes survival and proliferation of Schwann cells. In contrast, activation of caspase 3, a cysteine protease, is considered as a marker for apoptosis in Schwann cells. In the present study, axonal outgrowth, activation of ERK1/2 by phosphorylation (p-ERK 1/2 ) and immunoreactivity of cleaved caspase 3 were examined after immediate, delayed, or no repair of transected rat sciatic nerves.

Injury-induced activation of ERK 1/2 in the sciatic nerve of healthy and diabetic rats.

Phosphorylation of extracellular-signal-regulated kinase 1/2 (p-ERK 1/2) was investigated by immunohistochemistry at 30 min, 1 h, and 48 h after nerve transection in the sciatic nerve of healthy and diabetic [streptozotocin (STZ)-induced diabetes mellitus and BioBreeding (BB; i.e. DR.

Partial urethral obstruction: ATF3 and p-c-Jun are involved in the growth of the detrusor muscle and its motor innervation.

Objective: Infravesical obstruction leads to growth of urinary bladder smooth-muscle cells. The ganglion cells innervating the bladder muscle also increase in size. Stretch of detrusor muscle cells rapidly activates c-Jun NH₂-terminal kinase (JNK), which phosphorylates the transcription factor c-Jun, and stimulates the synthesis of the cotranscription factor ATF3.

Crossed over repair of the femoral sensory and motor branches influences N-CAM.

N-CAM, expressed by non-myelinating Schwann cells, was investigated by immunohistochemistry in transected rat femoral nerves, which were repaired either using a straight or a crossed over technique. N-CAM staining covered 30 and 11% of the cross-sectional area of sensory and motor branches, respectively, in uninjured nerves. After 3 days there was a transient smaller area of N-CAM staining following both the repairs.

Nanofluidics in hollow nanowires.

We present a novel scheme for producing nanotube membranes using free-standing hollow nanowires, with easily controllable dimensions. GaAs-AlInP core-shell nanowires were grown by metal-organic vapor phase epitaxy and were partially embedded in a polymer film. The GaAs core and substrate were etched selectively, leaving tubes with open access to both sides of the membrane.

Fifteen-piconewton force detection from neural growth cones using nanowire arrays.

We used epitaxially grown monodisperse nanowire arrays to measure cellular forces with a spatial resolution of 1 mum. Nerve cells were cultured on the array and cellular forces were calculated from the displacement of the nanowire tips. The measurements were done in situ on live cells using confocal microscopy.

Cell guidance by magnetic nanowires.

The phenomenon of contact guidance on thin fibers has been known since the beginning of the 20th century when Harrison studied cells growing on fibers from spider's web. Since then many studies have been performed on structured surfaces and fibers. Here we present a new way to induce guidance of cells or cell processes using magnetic nanowires.

Chapter 28: Future perspective in peripheral nerve reconstruction.

Nerve injuries induce severe disability and suffering for patients. Profound alterations in nerve trunks, neurons, and the central nervous system are induced rapidly after injury. This includes activation of intracellular signal transduction mechanisms aiming at the transfer of the cells into a regenerative state through the induction of the appropriate gene programs.

Delayed nerve repair increases number of caspase 3 stained Schwann cells.

Caspase 3 staining in Schwann cells was investigated with immunohistochemistry, as a measure of Schwann cell apoptosis, after transection and immediate (day 0) or delayed rat sciatic nerve repair (30, 90 and 180 days post injury). Cleaved caspase 3 stained Schwann cells significantly increased at the site of lesion (SNL; median [IQR], 15.2 [7.

Rectifying and sorting of regenerating axons by free-standing nanowire patterns: a highway for nerve fibers.

We present an EBL-defined nanowire pattern that can sort axons coming from different directions on a substrate. The pattern defines tracks for left-bound traffic and right-bound traffic, which opens up new possibilities for designing neural networks on a chip.

Porous silicon as a potential electrode material in a nerve repair setting: Tissue reactions.

We compared porous silicon (pSi) with smooth Si as chip-implant surfaces in a nerve regeneration setting. Silicon chips can be used for recording neural activity and are potential nerve interface devices. A silicon chip with one smooth and one porous side inserted into a tube was used to bridge a 5 mm defect in rat sciatic nerve.

Vascular endothelial growth factor in central nervous system injuries - a vascular growth factor getting nervous?

Vascular Endothelial Growth Factor (VEGF) is recognized as a central factor in growth, survival and permeability of blood vessels in both physiological and pathological conditions. It is as such of importance for vascular responses in various central nervous system (CNS) disorders. Accumulating evidence suggest that VEGF may also act as a neuroprotective and neurotrophic factor supporting neuronal survival and neuronal regeneration.

Costimulation blockade in transplantation of nerve allografts: long-term effects.

Costimulation blockade can prevent rejection of nerve allografts in short-term studies. We tested if costimulation blockade also prevented rejection of nerve allografts in long-term experiments, thereby improving functional recovery. A 7-mm sciatic nerve defect in C57/BL6 mice was bridged either by nerve allografts from Balb/C mice or by isogenic nerve grafts (isografts) from C57/BL6 mice.

Axonal guidance on patterned free-standing nanowire surfaces.

We demonstrate high-fidelity guidance of axons using rows of nanowires. The axons are prevented from crossing the rows, making it possible to guide and sort a large number of axons as opposed to when chemical patterns are used. Focal adhesion forms at the nanowires establishing a possible site of information transfer between the surface and the cells.

The influence of porous silicon on axonal outgrowth in vitro.

xonal outgrowth on smooth and porous silicon surfaces was studied in organ culture. The pore size of the silicon substrata varied between 100 and 1500 nm. We found that axons preferred to grow and elongate on porous silicon surfaces only when pores of (150-500 nm) are available.

Gallium phosphide nanowires as a substrate for cultured neurons.

Dissociated sensory neurons were cultured on epitaxial gallium phosphide (GaP) nanowires grown vertically from a gallium phosphide surface. Substrates covered by 2.5 microm long, 50 nm wide nanowires supported cell adhesion and axonal outgrowth.

Induction of activating transcription factor 3 after different sciatic nerve injuries in adult rats.

Staining by activating transcription factor 3 (ATF3), a neuronal marker of nerve injury, was examined by immunocytochemistry in neurons and Schwann cells after crush or transection (regeneration inhibited) of rat sciatic nerve. ATF3 immunoreactivity peaked in neurons after three days and then gradually subsided to normal within 12 weeks after the crush. The response lasted somewhat longer and declined over time in spinal cord neurons but not in those of dorsal root ganglia (DRG) after transection, indicating a differential regulation of sensory and motor neurons.

Calpain activation and apoptosis in motor neurons of cultured adult mouse spinal cord.

Calpain, a Ca2+-dependent cysteine protease, has been implicated in neuronal apoptosis following spinal cord injury. In this study, activation of calpain was investigated in motor neurons of adult spinal cord slices from the mouse, using a cell-permeable fluorogenic calpain substrate and Western blotting. Calpain was rapidly activated in the motor neurons of excised spinal cord slices and calpain activity was observed both in the cytoplasm and the nuclei.

Immunomodulation by costimulation blockade inhibits rejection of nerve allografts.

The aim of this study was to investigate if costimulation blockade could be used to modulate the immune response, to prevent rejection, and to stimulate regeneration into nerve allografts. Nerve allografts from Balb/C mice, and isogenic nerve grafts (isografts) from C57/BL6 mice, were used to bridge a 7-mm gap of the sciatic nerve in C57/BL6 mice. Allograft recipients were treated with either a triple treatment with anti-lymphocyte function antigen-1 (anti-LFA), anti-CD40 ligand (anti-CD40L), and cytotoxic T-lymphocyte antigen 4 immunoglobulin (anti-CTLA4Ig) or isotype antibodies (placebo) at postoperative days 0, 2, 4, and 6 (intraperitoneal).