A measure of the blink reflex to parametric variation of mechanical stimulation of the trigeminal nerve.

The primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5-60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable increase in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This increase was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity.

Protective Effects of Estrogen via Nanoparticle Delivery to Attenuate Myelin Loss and Neuronal Death after Spinal Cord Injury.

Spinal cord injury (SCI) is associated with devastating neurological deficits affecting more than 11,000 Americans each year. Although several therapeutic agents have been proposed and tested, no FDA-approved pharmacotherapy is available for SCI treatment. We have recently demonstrated that estrogen (E2) acts as an antioxidant and anti-inflammatory agent, attenuating gliosis in SCI. We have also demonstrated that nanoparticle-mediated focal delivery of E2 to the injured spinal cord decreases lesion size, reactive gliosis, and glial scar formation. The current study tested in vitro effects of E2 on reactive oxygen species (ROS) and calpain activity in microglia, astroglia, macrophages, and fibroblasts, which are believed to participate in the inflammatory events and glial scar formation after SCI. E2 treatment decreased ROS production and calpain activity in these glial cells, macrophages, and fibroblast cells in vitro. This study also tested the efficacy of fast- and slow-release nanoparticle-E2 constructs in a rat model of SCI. Focal delivery of E2 via nanoparticles increased tissue distribution of E2 over time, attenuated cell death, and improved myelin preservation in injured spinal cord. Specifically, the fast-release nanoparticle-E2 construct reduced the Bax/Bcl-2 ratio in injured spinal cord tissues, and the slow-release nanoparticle-E2 construct prevented gliosis and penumbral demyelination distal to the lesion site. These data suggest this novel E2 delivery strategy to the lesion site may decrease inflammation and improve functional outcomes following SCI.

The Pathophysiology of Osteoporosis after Spinal Cord Injury.

Spinal cord injury (SCI) affects approximately 300,000 people in the United States. Most individuals who sustain severe SCI also develop subsequent osteoporosis. However, beyond immobilization-related lack of long bone loading, multiple mechanisms of SCI-related bone density loss are incompletely understood. Recent findings suggest neuronal impairment and disability may lead to an upregulation of receptor activator of nuclear factor-κB ligand (RANKL), which promotes bone resorption. Disruption of Wnt signaling and dysregulation of RANKL may also contribute to the pathogenesis of SCI-related osteoporosis. Estrogenic effects may protect bones from resorption by decreasing the upregulation of RANKL. This review will discuss the current proposed physiological and cellular mechanisms explaining osteoporosis associated with SCI. In addition, we will discuss emerging pharmacological and physiological treatment strategies, including the promising effects of estrogen on cellular protection.

Respiratory outcomes with the use of a lower custom fit genioglossal-effecting oral appliance.

OBJECTIVE: Sleep apnea research cites that an oral appliance, which places the mandible in a more forward position and the genioglossus (tongue muscle) on the floor of the mouth, improves aspects of the pharyngeal opening. Exercise science research has cited improvements in airway dynamics and physiological variables with oral appliance use during exercise. Thus, the purpose of this study was to design an oral appliance that would act on the genioglossus and determine if there were effects on respiratory parameters while exercising. MATERIALS AND METHODS: Seventeen healthy subjects ages 18-43 participated in this study. Prior to the exercise protocol, the order of the oral applicance (OA) or no oral appliance (no OA) condition was randomly assigned to subjects, with subjects completing both conditions. Respiratory parameters (respiratory rate, ventilation, oxygen, and carbon dioxide) were measured between conditions while subjects ran for 10 min at steady state. RESULTS: The results demonstrated that both respiratory rate (25.97 BPM, OA and 28.35 BPM, no OA) and ventilation (47.66 l/min, OA and 50.34 l/min, No OA) were significantly lowered (p < .01) in the OA condition. There were no differences in carbon dioxide (1.89 l/min, no OA and 1.88 l/min, OA) or oxygen outcomes (2.17 l/min, no OA and 2.17 l/min OA). DISCUSSION: The outcomes from this study suggest that the design of the oral appliance elicits an effect on the genioglossus, thereby resulting in lowered respiratory rate and ventilation with no negative effects on oxygen uptake during exercise.

Development of a Non-Invasive Blink Reflexometer.

Qualitative assessments of the blink reflex are used clinically to assess neurological status in critical care, operating room, and rehabilitative settings. Despite decades of literature supporting the use of quantitative measurements of the blink reflex in the evaluation of multiple neurological disorders, clinical adoption has failed. Thus, there remains an unmet clinical need for an objective, portable, non-invasive metric of neurological health that can be used in a variety of settings. We have developed a high-speed videography-based device to trigger, record, and analyze a blink reflex. A pilot study was performed to compare the device's measurements to the published literature of electromyographic measurements, currently the gold standard. The study results indicate that the device is a viable tool to obtain fast, objective, and quantitative metrics of a blink reflex, and has promise as a non-invasive diagnostic assessment of neurological health.

Effects of various mouthpieces on respiratory physiology during steady-state exercise in college-aged subjects.

Protective mouthpieces have been used in a variety of sports to decrease the risk of orofacial injury. There are limited data to suggest that mouthpiece use during exercise may also provide an ergogenic effect. The aim of the present study was to investigate the effects of 3 different mouthpiece designs-boil-and-bite (BB) mouthpiece, ethylene vinyl acetate (EVA) custom mandibular mouthpiece, and polypropylene (Poly) custom mandibular mouthpiece-on respiratory physiology parameters and compare them with results of a no-mouthpiece (NM) condition. Sixteen college-aged, recreationally fit subjects ran for 10 minutes in 4 separate trials; mouthpiece conditions were randomly assigned to each trial for all subjects. Respiratory and cardiorespiratory measures, including oxygen uptake, carbon dioxide exhalation, ventilation, heart rate, tidal volume, and respiratory rate (RR), were assessed throughout testing. A repeated-measures analysis of variance indicated that RR was significantly lower (P = 0.04) in the BB mouthpiece condition (27.92 breaths per minute [BPM]) than in the NM condition (30.63 BPM). In paired t tests between conditions, the RR demonstrated in the BB condition (27.92 BPM) was significantly lower (P = 0.04) than that of each other condition (NM, 30.63 BPM; EVA, 29.92 BPM; and Poly, 29.92 BPM). The outcomes of the present study demonstrate that the use of the BB mouthpiece decreased RR during exercise. The differences cited between conditions may be attributed to the design of the mouthpiece and its mandibular placement as well as the activity of the genioglossus muscle. However, future studies should assess these parameters to determine the plausibility of these theories.

The effects of mouthpiece use on cortisol levels during an intense bout of resistance exercise.

Research has suggested mouthpiece use during exercise results in an increase in muscle strength and endurance. However, the research is difficult to replicate, and the methodology suggested measures that were too subjective to determine a mouthpiece effect. Thus, the purpose of this study was to use an objective measure to determine a possible physiological mechanism occurring during and after exercise with mouthpiece use. A within-subjects design was used in which 28 division I football players, aged 18-22 years, performed 2 identical bouts of a 1-hour intense resistance exercise, with each subject being randomly assigned the use of a custom-fit mouthpiece either during the first or second session. During both exercise sessions, saliva was analyzed for cortisol at the following time points: pre-exercise, 25, 45, and 60 minutes of exercise, and 10 minutes postexercise. The results revealed a significant difference in cortisol levels with the use of a mouthpiece vs. no mouthpiece (p = 0.019) at 10 minutes postexercise. Additionally, although the expected increase in cortisol levels from pre to 10 minutes postexercise was present in the no-mouthpiece group (p = 0.01), no such increase was observed in the mouthpiece group. These observations are most likely because of the decrease in cortisol from post to 10 minutes post (p = 0.04) in the mouthpiece group. These data demonstrate that although cortisol continued to increase in the no-mouthpiece session, there was a significant decrease in cortisol in the no-mouthpiece condition 10 minutes postexercise.

The effects of mouthpiece use on gas exchange parameters during steady-state exercise in college-aged men and women.

BACKGROUND: The authors conducted a study to assess the effects of custom-fitted mouthpieces on gas exchange parameters, including volume of oxygen consumption over time [corrected] (VO(2)), volume of oxygen consumption over time per kilogram of body weight [corrected] (VO(2) /kg) and volume of carbon dioxide production over time [corrected] (VO(2)). METHODS: Sixteen physically fit college students aged 18 through 21 years performed two 10-minute treadmill runs (6.5 miles per hour, 0 percent grade) for each of three treatment conditions (mouthpiece, no mouthpiece and nose breathing). The authors assigned the conditions randomly for each participant and for each session. They assessed gas exchange parameters by using a metabolic measurement system. RESULTS: The authors used analysis of variance to compare all variables. They set the significance level at α = .05 and used a Tukey post hoc analysis of treatment means to identify differences between groups. The results showed significant improvements (P < .05) in VO(2,) VO(2) /kg and VCO(2) in the mouthpiece condition. CONCLUSIONS: The study findings show that use of a custom-fitted mouthpiece resulted in improved specific gas exchange parameters. The authors are pursuing further studies to explain the mechanisms involved in the improved endurance performance exhibited with mouthpiece use. CLINICAL IMPLICATIONS: Dental care professionals have an obligation to understand the increasing research evidence in support of mouthpiece use during exercise and athletic activity and to educate their patients.

Effects of mouthpiece use on auditory and visual reaction time in college males and females.

Studies in exercise science have suggested that the use of a mouthpiece can improve performance, and these improvements may be linked to an enhancement in temporomandibular joint (TMJ) positioning. Studies have suggested that by improving TMJ positioning, there is improved blood flow in the area of the TMJ. Changes in TMJ positioning may be improved with an oral device. The purpose of this study was to determine if there were improvements in auditory and visual reaction time with the use of a boil and bite mouthpiece. Using a BIOPAC system, study participants (N = 34) were asked to respond to an auditory signal during 40 trials. In the visual reaction time test, participants (N = 13) were assessed on how quickly they responded to a computer cue for a total of 30 trials. Auditory results showed a significant improvement with the use of a mouthpiece (241.44 ms) vs without a mouthpiece (249.94 ms). Visual results showed that participants performed slightly better with the mouthpiece (285.55 ms) vs without the mouthpiece (287.55 ms). These findings suggest that the use of mouthpiece positively affects visual and auditory reaction time, which is a vital aspect to optimal sport and exercise performance. Future studies should continue to shed light on possible reasons for the improvements in auditory and visual reaction time with the use of a mouthpeice. In addition, future studies should further illuminate what, if any, connection these improvements have with enhanced TMJ positioning.

Effects of mouthpiece use on airway openings and lactate levels in healthy college males.

Research has described the use of mouthpieces not only in preventing oral-facial injuries, but linking use to improvements in muscular strength and endurance. However, the mechanisms by which these improvements occur have not been elucidated. The purpose of this study was to understand possible physiological explanations for improvements in exercise performance with the use of a mouthpiece. Specifically, this study focused on differences in lactate levels after 30 minutes of endurance exercise with and without a mouthpiece. In addition, computed tomography (CT) scans were taken of the cross-sectional area of the oropharynx in each participant (N = 10) with and without a mouthpiece. CT scans showed a significant difference in mean width (28.27 mm with the mouthpiece vs 25.93 mm without the mouthpiece, P = .029) and an increase in mean diameter with a mouthpiece (12.17 mm vs 11.21 mm, P = .096). Lactate levels were lowered with the mouthpiece at 1.86 mmol/L vs 2.72 mmol/L without mouthpiece. This research suggests that there is an improvement in endurance performance that may be linked to improved airway openings resulting from the use of a mouthpiece. Future studies should continue to clarify the possible mechanisms for these exercise outcomes as well as to understand the optimal mandibular advancement to elicit these exercise improvements.

Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca2+ influx.

Apoptosis of retinal ganglion cells (RGCs) impairs vision in glaucoma patients. RGCs are also degenerated in multiple sclerosis (MS), resulting in loss of visual perception in MS patients. We examined the involvement of calpain and caspase cascades in apoptosis of the rat retinal ganglion cell line RGC-5 following 24 h of exposure to 250 nM ionomycin (IMN) or 300 units/ml interferon-gamma (IFN-gamma) and then evaluated functional neuroprotection with 2 microM calpeptin (CP, a calpain-specific inhibitor). Morphological and biochemical features of apoptosis were detected in RGC-5 cells following exposure to IMN or IFN-gamma. Fura-2 assay determined significant increases in intracellular free [Ca2+] following exposure to IMN or IFN-gamma. Pretreatment with CP for 1 h prevented Ca2+ influx, proteolytic activities, and apoptosis in RGC-5 cells. Western blot analyses showed an increase in activities of calpain and caspase-12, upregulation of Bax:Bcl-2 ratio, release of cytochrome c from mitochondria, and increase in caspase-9 and caspase-3 activities during apoptosis. Increased caspase-3 activity was also confirmed by a colorimetric assay. Activation of caspase-8 and cleavage of Bid to tBid in RGC-5 cells following exposure to IFN-gamma indicated co-operation between extrinsic and intrinsic pathways of apoptosis. Patch-clamp recordings showed that pretreatment with CP attenuated apoptosis and maintained normal whole-cell membrane potential, indicating functional neuroprotection. Taken together, our results demonstrated that Ca2+ overload could be responsible for activation of calpain and caspase cascades leading to apoptotic death of RGC-5 cells and CP provided functional neuroprotection.

Functional adaptability of muscle fibers to long-term resistance exercise.

PURPOSE: We compared the functional properties of muscle fibers from two groups of subjects that differed widely in their training history to investigate whether long-term resistance exercise alters the intrinsic contractile properties of skeletal muscle fibers. METHODS: Vastus lateralis muscle biopsies were obtained from six sedentary males (NT group, age = 23 +/- 1 yr) and six males who had participated in regular resistance exercise training over the preceding 7.6 +/- 1.6 yr (RT group, 22 +/- 1 yr). Chemically skinned muscle fiber segments were activated with a saturating free [Ca2+] to quantify fiber peak Ca2+-activated force (P(o)), unloaded shortening velocity (V(o)), and peak power. Fiber segment myosin heavy chain (MHC) isoform content was identified by gel electrophoresis. RESULTS: Slow and fast fibers from the RT group were larger in CSA and produced greater absolute P(o) and absolute peak power in comparison with fibers from the NT group. However, these differences were no longer evident after P(o) and peak power were normalized to fiber CSA and fiber volume, respectively. V(o)/fiber length was dependent on fiber MHC content but independent of training status. CONCLUSION: Fiber hypertrophy was sufficient to account for intergroup differences in P(o) and peak power of slow and fast fibers. There was no evidence that the intrinsic contractility of slow or fast fibers, as evaluated by force, shortening velocity, and power normalized to the appropriate fiber dimensions, differed between RT and NT groups.

Morphological and functional characteristics of skeletal muscle fibers from hormone-replaced and nonreplaced postmenopausal women.

We tested the hypothesis that cross-bridge mechanisms of contraction differed in early postmenopausal women who did or did not receive hormone replacement therapy (HRT). Vastus lateralis biopsies were obtained from 17 postmenopausal women (49-57 years old), 8 of whom were on HRT for the previous 24 +/- 5 months and 9 of whom were never on HRT. Electrophoresis and enzyme histochemistry revealed that fiber myosin heavy chain (MHC) isoform distribution, the cross-sectional area (CSA) of slow and fast fibers, and the relative CSA occupied by each, were similar for HRT and non-HRT groups. Single permeabilized fibers containing type IIa MHC had greater Ca(2+)-activated peak specific force, unloaded shortening velocity, and peak power than fibers containing type I MHC, but in all cases the values for HRT and non-HRT groups were similar. In this cross-sectional study, we found no evidence that Ca(2+)-activated fiber function, MHC isoform distribution, or relative CSA occupied by slow and fast fibers differed between HRT and non-HRT groups.

Functional properties of human muscle fibers after short-term resistance exercise training.

The aim of this study was to assess the relationships between human muscle fiber hypertrophy, protein isoform content, and maximal Ca(2+)-activated contractile function following a short-term period of resistance exercise training. Six male subjects (age 27 +/- 2 yr) participated in a 12-wk progressive resistance exercise training program that increased voluntary lower limb extension strength by >60%. Single chemically skinned fibers were prepared from pre- and posttraining vastus lateralis muscle biopsies. Training increased the cross-sectional area (CSA) and peak Ca(2+)-activated force (P(o)) of fibers containing type I, IIa, or IIa/IIx myosin heavy chain by 30-40% without affecting fiber-specific force (P(o)/CSA) or unloaded shortening velocity (V(o)). Absolute fiber peak power rose as a result of the increase in P(o), whereas power normalized to fiber volume was unchanged. At the level of the cross bridge, the effects of short-term resistance training were quantitative (fiber hypertrophy and proportional increases in fiber P(o) and absolute power) rather than qualitative (no change in P(o)/CSA, V(o), or power/fiber volume).