The purpose of this study was to evaluate the degree of functional recovery in adult rats with completely transected spinal cord following experimental treatment regimens that include implantation of peripheral nerve segments and local application of acidic fibroblast growth factor (aFGF). Rats were randomly divided to five groups: (1) spinal cord transection, (2) spinal cord transection and aFGF treatment, (3) spinal cord transection and peripheral nerve grafts, (4) spinal cord transection, aFGF treatment, and peripheral nerve grafts, and (5) sham control (laminectomy only). The locomotor behavior of all rats was analyzed by the Basso, Beattie and Bresnahan (BBB) open field locomotor test over the six months survival time. Immunohistochemisty for neurofilament protein, and somatosensory (SSEP) and motor evoked potentials (MEP) were used to evaluate axon growth across the damage site following the different treatments. The results show four principal findings: (1) Only the combination of peripheral nerve grafts and aFGF treatment improved hindlimb locomotor function after spinal cord transection. (2) The SSEP and MEP demonstrated electrophysiological evidence of both sensory and motor information crossing the damaged site, but only in the combined nerve grafts and aFGF treatment rats. (3) Immunostaining demonstrated neurofilament positive axons extending through the graft area and into distal end of spinal cord, but only in the group with combined nerve grafts and aFGF treatment. (4) Retransection of group 4 rats eliminated the behavioral recovery, MEP, and SSEP responses, indicating that the improvement of hindlimb locomotor activity came from supraspinal control. These results demonstrate the ability of the repair strategy combining peripheral nerve grafts and aFGF treatment to facilitate the regeneration of spinal ascending and descending tracts and also recovery of motor behavior following spinal cord injury.
Behavioral assessments of hindlimb motor recovery and anatomical assessments of extended axons of long spinal tracts were conducted in adult rats following complete spinal cord transection. Rats were randomly divided into 3 groups: 1) sham control group (laminectomy only; n = 12); 2) transection-only group, spinal cord transection at T8 (n = 20); and 3) experimental treatment group, spinal cord transection at T8, with peripheral nerve grafts (PNG) and application of acidic fibroblast growth factor (aFGF) (n = 14). The locomotor behavior and stepping of all rats were analyzed over a 6-month survival time using the Basso, Beattie, Bresnahan (BBB) open field locomotor test and the contact placing test. Immunohistochemistry for serotonin (5-HT), anterograde tracing with biotinylated dextran amine (BDA), and retrograde tracing with fluoro-gold were used to evaluate the presence of axons below the damage site following treatment. When compared with the transection-only group, the nerve graft with the aFGF group showed 1) significant improvement in hindlimb locomotion and stepping, 2) the presence of 5-HT-labeled axons below the lesion site at lumbar cord level (these were interpreted as regenerated axons from the raphe nuclei), 3) the presence of anterograde BDA labeling of corticospinal tract axons at the graft site and below, and 4) fluoro-gold retrograde labeling of neuron populations in motor cortex and in red nucleus, reticulospinal nuclei, raphe nuclei, and vestibular nuclei. We conclude that peripheral nerve grafts and aFGF treatments facilitate the regrowth of the spinal axons and improve hindlimb function in a T-8 spinal cord-transected rat model.
The purpose of this study was to assess the effectiveness of functional magnetic stimulation (FMS) for producing expiratory function in normal human subjects. Twelve able-bodied normal subjects were recruited for this study. FMS of the expiratory muscles was performed by using a magnetic stimulator and placing the magnetic coil along the lower thoracic spine. Results showed that peak expired pressure, volume, and flow rate generated by FMS at the end of normal inspiration (102.5 +/- 13.62 cmH2O, 1.6 +/- 0.16 liters, and 4.8 +/- 0.35 l/s, respectively) were comparable to their voluntary maximal levels (P > 0.1). The optimal coil placement was between T7 and T11, and the optimal stimulation parameters were a frequency of 25 Hz and 70-80% of maximal intensity. We conclude that 1) FMS of the lower thoracic nerves in normal subjects resulted in a significant expiratory function comparable to their voluntary maximum; 2) FMS was noninvasive and was well tolerated by all subjects; and 3) FMS may be useful to produce cough in patients in critical care or perioperative settings, or in patients with neurological disorders.
Our studies have demonstrated effective stimulation of the bladder, bowel, and expiratory muscles in patients with spinal cord injury using functional magnetic stimulation. However, one limitation of the magnetic coils (MC) is related to their inability to specifically stimulate the target tissue without activation of surrounding tissue. The primary goal of this study was to determine the governing parameters in the MC design, such as coil configuration, diameter, and number of turns in one loop of the coil. By varying these parameters, our approach was to design, construct, and evaluate the induced electric field distributions of two sets of novel MC's. Based on the slinky coil design, the first set of coils was constructed to compare their abilities in generating induced electric fields for focal nerve excitation. The second set of coils was built to determine the effect that changes in two parameters, coil diameter and number of turns in one loop, had on field penetration. The results showed that the slinky coil design produced more focalized stimulation when compared to the planar round coils. The primary-to-secondary peak ratios of the induced electric field from slinky 1 to 5 were 1.00, 2.20, 2.85, 2.62, and 3.54. We also determined that coils with larger diameters had better penetration than those with smaller diameters. Coils with less number of turns in one loop had higher initial field strengths; when compared to coils that had more turns per loop, initial field strengths remained higher as distance from the coil increased. In our attempt to customize MC design according to each functional magnetic stimulation application and patients of different sizes, the parameters of MC explored in this study may facilitate designing an optimal MC for a certain clinical application.
Abstract. Mixed-phase Southern Ocean clouds are challenging to simulate, and their representation in climate models is an important control on climate sensitivity. In particular, the amount of supercooled water and frozen mass that they contain in the present climate is a predictor of their planetary feedback in a warming climate. The recent Southern Ocean Clouds, Radiation, Aerosol Transport Experimental Study (SOCRATES) vastly increased the amount of in situ data available from mixed-phase Southern Ocean clouds useful for model evaluation. Bulk measurements distinguishing liquid and ice water content are not available from SOCRATES, so single-particle phase classifications from the Two-Dimensional Stereo (2D-S) probe are invaluable for quantifying mixed-phase cloud properties. Motivated by the presence of large biases in existing phase discrimination algorithms, we develop a novel technique for single-particle phase classification of binary 2D-S images using a random forest algorithm, which we refer to as the University of Washington Ice–Liquid Discriminator (UWILD). UWILD uses 14 parameters computed from binary image data, as well as particle inter-arrival time, to predict phase. We use liquid-only and ice-dominated time periods within the SOCRATES dataset as training and testing data. This novel approach to model training avoids major pitfalls associated with using manually labeled data, including reduced model generalizability and high labor costs. We find that UWILD is well calibrated and has an overall accuracy of 95 % compared to 72 % and 79 % for two existing phase classification algorithms that we compare it with. UWILD improves classifications of small ice crystals and large liquid drops in particular and has more flexibility than the other algorithms to identify both liquid-dominated and ice-dominated regions within the SOCRATES dataset. UWILD misclassifies a small percentage of large liquid drops as ice. Such misclassified particles are typically associated with model confidence below 75 % and can easily be filtered out of the dataset. UWILD phase classifications show that particles with area-equivalent diameter (Deq) < 0.17 mm are mostly liquid at all temperatures sampled, down to −40 ∘C. Larger particles (Deq>0.17 mm) are predominantly frozen at all temperatures below 0 ∘C. Between 0 and 5 ∘C, there are roughly equal numbers of frozen and liquid mid-sized particles (0.17<Deq<0.33 mm), and larger particles (Deq>0.33 mm) are mostly frozen. We also use UWILD's phase classifications to estimate sub-1 Hz phase heterogeneity, and we show examples of meter-scale cloud phase heterogeneity in the SOCRATES dataset.
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