AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.

More than half of spinal cord injury (SCI) cases occur in the cervical region, leading to respiratory dysfunction due to damaged neural circuitry that controls critically important muscles such as the diaphragm. The C3-C5 spinal cord is the location of phrenic motor neurons (PhMNs) that are responsible for diaphragm activation; PhMNs receive bulbospinal excitatory drive predominately from supraspinal neurons of the rostral ventral respiratory group (rVRG). Cervical SCI results in rVRG axon damage, PhMN denervation, and consequent partial-to-complete paralysis of hemidiaphragm. In a rat model of C2 hemisection SCI, we expressed the axon guidance molecule, brain-derived neurotrophic factor (BDNF), selectively at the location of PhMNs (ipsilateral to lesion) to promote directed growth of rVRG axons toward PhMN targets by performing intraspinal injections of adeno-associated virus serotype 2 (AAV2)-BDNF vector. AAV2-BDNF promoted significant functional diaphragm recovery, as assessed by in vivo electromyography. Within the PhMN pool ipsilateral to injury, AAV2-BDNF robustly increased sprouting of both spared contralateral-originating rVRG axons and serotonergic fibers. Furthermore, AAV2-BDNF significantly increased numbers of putative monosynaptic connections between PhMNs and these sprouting rVRG and serotonergic axons. These findings show that targeting circuit plasticity mechanisms involving the enhancement of synaptic inputs from spared axon populations is a powerful strategy for restoring respiratory function post-SCI.-Charsar, B. A., Brinton, M. A., Locke, K., Chen, A. Y., Ghosh, B., Urban, M. W., Komaravolu, S., Krishnamurthy, K., Smit, R., Pasinelli, P., Wright, M. C., Smith, G. M., Lepore, A. C. AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.

Effect of Temperature and Process on Quantity and Composition of Laboratory-generated Bitumen Emissions.

In this study we investigated the impact of temperature on emissions as related to various bitumen applications and processes used in commercial products. Bitumen emissions are very complex and can be influenced in quantity and composition by differences in crude source, refining processes, application temperature, and work practices. This study provided a controlled laboratory environment to study five bitumen test materials from three European refineries; three paving grade, one used for primarily roofing and some paving applications, and one oxidized industrial specialty bitumen. Emissions were generated at temperatures between 140°C and 230°C based on typical application temperatures of each product. Emissions were characterized by aerodynamic particle size, total organic matter (TOM), simulated distillation, 40 individual PACs, and fluorescence (FL-PACs) spectroscopy. Results showed that composition of bitumen emissions is influenced by temperature under studied experimental conditions. A distinction between the oxidized bitumen with flux oil (industrial specialty bitumen) and the remaining bitumens was observed. Under typical temperatures used for paving (150°C-170°C), the TOM and PAC concentrations in the emissions were low. However, bitumen with flux oil produced significantly higher emissions at 230°C, laden with high levels of PACs. Flux oil in this bitumen mixture enhanced release of higher boiling-ranged compounds during application conditions. At 200°C and below, concentrations of 4-6 ring PACs were ≤6.51 µg/m(3) for all test materials, even when flux oil was used. Trends learned about emission temperature-process relationships from this study can be used to guide industry decisions to reduce worker exposure during processing and application of hot bitumen.