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Objective: Degenerative changes of the cervical spinal column are the most common cause of spinal cord lesions in the elderly. Conventional clinical, electrophysiological and radiological diagnostics of spinal cord compression are often inconsistent. Methods: The feasibility and diagnostic potential[for full text, please go to the a.m. URL], 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Background Degenerative changes of the cervical spinal column are the most common cause of spinal cord lesions in the elderly. Conventional clinical, electrophysiological and radiological diagnostics of spinal cord compression are often inconsistent. Materials and methods The feasibility and diagnostic potential of a novel T1 mapping method at 0.5 mm resolution and 4 s acquisition time was evaluated in 14 patients with degenerative cervical spinal canal stenosis (SCS) and 6 healthy controls. T1 mapping was performed in axial sections of the stenosis as well as above and below. All subjects received standard T2-weighted MRI of the cervical spine (including SCS-grading 0-III), electrophysiological and clinical examinations. Results Patients revealed significantly decreased T1 relaxation times of the compressed spinal cord within the SCS (912 ± 53 ms, mean ± standard deviation) in comparison to unaffected segments above (1027 ± 39 ms, p, Highlights • Rapid T1 mapping at 0.5 mm resolution was tested in cervical spinal canal stenosis (SCS). • T1 relaxation times significantly decreased within the SCS. • T1 relaxation times were significantly lower in grade II vs grade I SCS. • Central conduction deficits were inversely correlated with T1 relaxation time. • Rapid T1 mapping robustly and accurately quantifies spinal cord compression.

alpha-Synuclein (alpha-Syn) is intimately linked to the etiology of Parkinson's Disease, as mutations and even subtle increases in gene dosage result in early onset of the disease. However, how this protein causes neuronal dysfunction and neurodegeneration is incompletely understood. We thus examined a comprehensive range of physiological parameters in cultured rat primary neurons overexpressing alpha-Syn at levels causing a slowly progressive neurodegeneration. In contradiction to earlier reports from non-neuronal assay systems we demonstrate that alpha-Syn does not interfere with essential ion handling capacities, mitochondrial capability of ATP production or basic electro-physiological properties like resting membrane potential or the general ability to generate action potentials. alpha-Syn also does not activate canonical stress kinase Signaling converging on SAPK/Jun, p38 MAPK or Erk kinases. Causative for alpha-Syn-induced neurodegeneration are mitochondrial thiol oxidation and activation of caspases downstream of mitochondrial outer membrane permeabilization, leading to apoptosis-like cell death execution with some unusual aspects. We also aimed to elucidate neuroprotective strategies counteracting the pathophysiological processes caused by alpha-Syn. Neurotrophic factors, calpain inhibition and increased lysosomal protease capacity showed no protective effects against alpha-Syn overexpression. In contrast, the major watchdog of outer mitochondrial membrane integrity, Bcl-Xl, was capable of almost completely preventing neuron death, but did not prevent mitochondrial thiol oxidation. Importantly, independent from the quite mono-causal induction of neurotoxicity, alpha-Syn causes diminished excitability of neurons by external stimuli and robust impairments in endogenous neuronal network activity by decreasing the frequency of action potentials generated without external stimulation. This latter finding suggests that alpha-Syn can induce neuronal dysfunction independent from its induction of neurotoxicity and might serve as an explanation for functional deficits that precede neuronal cell loss in synucleopathies like Parkinson's disease or dementia with Lewy bodies.

Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (alpha Syn-WT), a protein associated with PD, and its mutant variants alpha Syn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of alpha Syn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of alpha Syn-WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with alpha Syn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all alpha Syn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by alpha Syn-WT and -A53T but not by alpha Syn-A30P. Correspondingly, colocalization of alpha Syn and the autophagy marker LC3 was reduced for alpha Syn-A30P compared with the other alpha Syn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both alpha Syn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that alpha Syn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered.

he Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy. Open-Access-Publikationsfonds 2014 peerReviewed

27th European Photovoltaic Solar Energy Conference and Exhibition; 888-895, The interface passivation of a-AlOx/a-SiNx:H stacks deposited on p-type silicon by in-line plasma enhanced chemical vapor deposition is investigated by means of charge carrier lifetime, field dependent surface photovoltage and capacitance voltage measurements as well as Fourier transform infrared spectroscopy. To control the quality of the interface, we performed different wet chemical surface preparation steps prior to a-AlOx/a-SiNx:H stack deposition. Our investigation is focusing on the interface passivation upon post-deposition thermal treatments such as annealing at 425 °C and firing at 860 °C as applied in the silicon solar cell industry. We demonstrate that the interface recombination is mainly controlled by the interface state density as demonstrated by the correlation between the surface recombination velocity and interface state density inferred from lifetime and SPV measurements. The increase of the negative charge density after thermal steps as revealed by capacitance-voltage measurements correlates with the increase of the density of negatively charged AlO4 tetrahedra as revealed by infrared spectroscopy suggesting that the tetrahedrally coordinated Al contribute to the formation of the negative charge.

26th European Photovoltaic Solar Energy Conference and Exhibition; 2141-2145, In this paper, influences of pulse duration and surface topography on laser ablation of silicon nitride layers on thin emitters were investigated. For the first time, the pulse duration dependent threshold fluence and the pulse duration dependent laser-induced damage were studied by using an IR laser system with tunable pulse duration. For all pulse durations, bare silicon was observed in the ablated regions. A linear increase of the threshold fluence with pulse duration was determined. The reason for this is an increase of the probability of multi-photon-absorption (MPA) in silicon at shorter pulse durations. Furthermore, a pulse duration dependent laser-induced damage is observed. Differences in damage characteristics between planar and textured surfaces were also observed. On textured samples losses in the open circuit voltage Voc of at least 40 % were determined. In contrast, on planar samples much lower losses in Voc were determined.