Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system functions after developmental exposure to ethanol vapors.

Ethanol-blended gasoline entered the market in response to demand for domestic renewable energy sources, and may result in increased inhalation of ethanol vapors in combination with other volatile gasoline constituents. It is important to understand potential risks of inhalation of ethanol vapors by themselves, and also as a baseline for evaluating the risks of ethanol combined with a complex mixture of hydrocarbon vapors. Because sensory dysfunction has been reported after developmental exposure to ethanol, we evaluated the effects of developmental exposure to ethanol vapors on neurophysiological measures of sensory function as a component of a larger project evaluating developmental ethanol toxicity. Pregnant Long-Evans rats were exposed to target concentrations 0, 5000, 10,000, or 21,000 ppm ethanol vapors for 6.5h/day over GD9-GD20. Sensory evaluations of male offspring began between PND106 and PND128. Peripheral nerve function (compound action potentials, nerve conduction velocity (NCV)), somatosensory (cortical and cerebellar evoked potentials), auditory (brainstem auditory evoked responses), and visual evoked responses were assessed. Visual function assessment included pattern elicited visual evoked potentials (VEPs), VEP contrast sensitivity, and electroretinograms recorded from dark-adapted (scotopic), light-adapted (photopic) flashes, and UV flicker and green flicker. No consistent concentration-related changes were observed for any of the physiological measures. The results show that gestational exposure to ethanol vapor did not result in detectable changes in peripheral nerve, somatosensory, auditory, or visual function when the offspring were assessed as adults.

Selection of biomaterials for peripheral nerve regeneration using data from the nerve chamber model.

Peripheral nerve regeneration has been studied in a variety of animal models. Of these, the nerve chamber model has clearly dominated. It has been used to generate a large base of data that, however, cannot be analyzed usefully due to lack of standardization of experimental conditions and assays. Lack of standardization of critical experimental parameters of the model has, however, greatly limited the opportunity to compare directly data from independent investigators; as a result, progress in understanding conditions for optimal nerve regeneration has been stunted. In this article, we provide an overview of the major experimental parameters that must be controlled in order to generate data from independent investigators that can be compared directly (normalized data). Such parameters include the gap length, animal species, and the identity of assays used to evaluate the product of the regenerative process. Use of the recently introduced concept of critical axon elongation, the gap length at which the probability of axonal outgrowth (reinnervation) across the gap is 50%, leads to generation of a normalized database that includes data from several independent investigators. Conclusions are drawn about the relative efficacy of the various biomaterials and devices employed. Nerve chamber configurations that had the highest regenerative activity were those in which the tube wall comprised collagen and certain synthetic biodegradable polymers rather than silicone, and was cell-permeable rather than protein-permeable. In addition, the following tube fillings showed very high regenerative activity: suspensions of Schwann cells; a solution either of acidic or basic fibroblast growth factor; insoluble ECM substrates rather than solutions or gels; polyamide filaments oriented along the tube axis; highly porous, insoluble analogs of the ECM with specific structure and controlled degradation rate.

Nerve growth dynamics. Quantitative models for nerve development and regeneration.

The quantitative analysis of nerve growth dynamics is critical to our understanding of nerve development and regeneration, but only recently has a quantitative framework begun to emerge to help define key objectives and to direct experimental measurements towards achieving this goal. Conceptually, the framework centers on the dynamic processes commonly observed for individual growth cones of growing neurites at the phase microscopy level, namely lamellipodial and filopodial extension and retraction. Because these activities essentially define the position of the axon tip, understanding how they are regulated offers to yield direct insight into factors governing the growth trajectory of the axon. In addition, much biological interest and effort is focused on the lamellipodial and filopodial behavior of the growth cone, which should facilitate experimental quantitation. Characterization of lamellipodial and filopodial activity has not been straightforward, however, because their inherent randomness leads to a requirement for considerable data and for less common mathematical techniques, such as time-series analysis. The work reviewed above has identified key analytical tools and experimental parameters needed to develop an integrated model of growth cone dynamics. Detailed measurement and analysis will be required to carry this development process to the next step. The cellular model of growth cone motility resulting from the characterization of lamellipodial and filopodial dynamics represents an intermediate description that can be extended to encompass both molecular mechanisms of growth cone behavior and axonal growth in multicellular tissue environments. For example, on the molecular level, filopodia contain a central core of actin filaments whose polymerization and depolymerization is thought to correspond to filopodial extension and retraction, with significant regulation possible through receptor-mediated effects on actin dynamics. By rewriting the parameters of filopodia dynamics in the current model in terms of these molecular events, one can begin to investigate their effects on growth cone behavior and to examine hypotheses of molecular mechanisms. Processes underlying lamellipodial behavior can be examined in a similar manner. At the tissue level, the effects of environmental factors on model parameters can be incorporated to yield predictions of the neurite outgrowth response to a particular environment. Such predictions offer a basis for designing microenvironments with optimal characteristics for enhancing nerve regeneration or manipulating the nerve growth response. Although the quantitative framework described here has focused on growth by peripheral nerve cells, it represents concepts known to apply to neurons of the central nervous system, as well.(ABSTRACT TRUNCATED AT 400 WORDS)