Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats

The importance of the in vivo dynamic nature of the circuitries within the spinal cord that generate locomotion is becoming increasingly evident. We examined the characteristics of hindlimb EMG activity evoked in response to epidural stimulation at the S1 spinal cord segment in complete midthoracic spinal cord-transected rats at different stages of postlesion recovery. A progressive and phase-dependent modulation of monosynaptic (middle) and long-latency (late) stimulation-evoked EMG responses was observed throughout the step cycle. During the first 3 weeks after injury, the amplitude of the middle response was potentiated during the EMG bursts, whereas after 4 weeks, both the middle and late responses were phase-dependently modulated. The middle- and late-response magnitudes were closely linked to the amplitude and duration of the EMG bursts during locomotion facilitated by epidural stimulation. The optimum stimulation frequency that maintained consistent activity of the long-latency responses ranged from 40 to 60 Hz, whereas the short-latency responses were consistent from 5 to 130 Hz. These data demonstrate that both middle and late evoked potentials within a motor pool are strictly gated during in vivo bipedal stepping as a function of the general excitability of the motor pool and, thus, as a function of the phase of the step cycle. These data demonstrate that spinal cord epidural stimulation can facilitate locomotion in a time-dependent manner after lesion. The long-latency responses to epidural stimulation are correlated with the recovery of weight-bearing bipedal locomotion and may reflect activation of interneuronal central pattern-generating circuits

Cosmos 2229

The 6 weeks preflight activities of the Cosmos project during 1993 included: modification of EMG connector to improve the reliability of EMG recording; 24 hour cage activity recording from all but two of the flight animals (monkeys); attempts to record from flight candidates during foot lever task; and force transducer calibrations on all flight candidate animals. The 4 week postflight recordings included: postflight recordings from flight animals; postflight recordings on 3 control (non-flight) animals; postflight recalibration of force transducers on 1 flight and 4 control (non-flight) animals; and attempts to record EMG and video data from the flight animals during postflight locomotion and postural activity. The flight EMG recordings suggest that significant changes in muscle control may occur in spaceflight. It is also clear from recordings that levels of EMG recorded during spaceflight can attain values similar to those measured on earth. Amplifier gain settings should therefore probably not be changed for spaceflight

Muscle Feasibility for Cosmos Rhesus

The following tasks were proposed for the Cosmos project: 1) Complete recordings of all preflight candidates during performance of a foot pedal motor control task while in the space capsule mock-up. 2) Complete recordings of all preflight candidates during locomotion and postural tasks. 3) Complete recordings of 24-hour spontaneous cage activity in the two flight monkeys before and after flight and of at least three control (non-flight) monkeys after the flight has been completed. 4) Complete recordings of the foot pedal and motor control tasks during flight and postflight as scheduled. 5) Complete recordings of the vertical drop test pre, during and postflight for the two flight and three control monkeys. 6) Complete recordings of locomotion and posture tests of the two flight monkeys postflight. 7) Complete recordings of locomotion and postural tests of at least three control (non-flight) monkeys during the postflight period. 8) Recalibrate buckles of the two flight and of at least three control monkeys postflight. 9) Complete analysis of the 24 hour EMG recordings of all monkeys. 10) Complete analysis of the foot pedal, locomotor and postural motor control tasks for the two flight and three control monkeys. It was proposed that efforts in the first postflight year be concentrated on the two flight animals and three postflight animals

Modulation Of Hsp25 And Tnf-alpha During The Early Stages Of Functional Overload Of A Rat Slow And Fast Muscle

Early events in response to abrupt increases in activation and loading with muscle functional overload (FO) are associated with increased damage and inflammation. Heat shock protein 25 (HSP25) may protect against these stressors. and its expression can be regulated by muscle loading and activation. The purpose of this study was to investigate the responses of HSP25. phosphorylated HSP25 (pHSP25), and tumor necrosis factor-alpha (TNF-alpha) during FO of the slow soleus and fast plantaris. We compared the HSP25 mRNA, HSP25 protein, pHSP25, and TNF-alpha responses in the soleus and plantaris after 0.5, 1, 2, 3, and 7 days of FO. HSP25 and pHSP25 were quantified in soluble and insoluble fractions. HSP25 mRNA increased immediately in both muscles and decreased with continued FO. However, HSP25 mRNA levels were consistently higher in the Muscles of FO than control rats. In the soluble fraction. HSP25 increased in the plantaris after 2-7 days of FO with the greatest response at 3 and 7 days. The pHSP25 response to FO was greater in the plantaris than soleus at all points in the soluble fraction and at 0.5 days in the insoluble fraction. TNF-alpha levels in the plantaris, but not soleus, were higher than control at 0.5-2 days of FO. This may have contributed to the greater FO response in pHSP25 in the plantaris than soleus as TNF-alpha increased pHSP25 in C2C12 myotubes. These results suggest that the initial responses of pHSP25 and TNF-alpha to mechanical stress and inflammation associated with FO are greater in a fast than slow extensor muscle

Regressed three-dimensional capillary network and inhibited angiogenic factors in the soleus muscle of non-obese rats with type 2 diabetes

Based on findings obtained using two-dimensional capillary analyses on tissue cross-sections, diabetes has been shown to be associated with a high risk for microangiopathy and capillary regression in skeletal muscles. We visualized the three-dimensional architecture of the capillary networks in the soleus muscle of non-obese Goto-Kakizaki (GK) rats with type 2 diabetes and compared them with those of control Wistar rats to provide novel information, e.g., capillary volume, on the capillary networks. In addition, we examined pro- and anti-angiogenic gene expression levels in the soleus muscle of GK rats using TaqMan probe-based real-time PCR. As expected, plasma glucose levels were higher and insulin levels lower in GK than control rats. The three-dimensional architecture of the capillary networks was regressed and capillary volume was smaller in the soleus muscle of GK compared to control rats. The mRNA expression levels of the pro-angiogenic factors HIF-1α, KDR, Flt-1, ANG-1, and Tie-2 were lower, whereas the level of the anti-angiogenic factor TSP-1 was higher in GK than control rats. These data suggest that a decrease in pro-angiogenic and increase in anti-angiogenic factors may play an important role in type 2 diabetes-induced muscle circulatory complications

Job Growth in Early Transition: Comparing Two Paths

Small start-up firms are the engine of job creation in early transition and yet little is known about the characteristics of this new sector. We seek to identify patterns of job growth in this sector in terms of niches left from central planning and ask about differences in job creation across two different transition economies: Estonia, which experienced rapid destruction of the pre-existing firms, and the Czech Republic, which reduced the old sector gradually. We find job growth within industries to be quantitatively more important than job growth due to across-industry reallocation. Furthermore, the industrial composition of startups is strikingly similar in the two countries. We offer convergence to "western" industry firm-size distributions as an explanation. We also find regularities in wage evolution across new and old firms, including small differences in job quality across the two transition paths.http://deepblue.lib.umich.edu/bitstream/2027.42/39888/3/wp503.pd

Effects of diet and/or exercise in enhancing spinal cord sensorimotor learning.

Given that the spinal cord is capable of learning sensorimotor tasks and that dietary interventions can influence learning involving supraspinal centers, we asked whether the presence of omega-3 fatty acid docosahexaenoic acid (DHA) and the curry spice curcumin (Cur) by themselves or in combination with voluntary exercise could affect spinal cord learning in adult spinal mice. Using an instrumental learning paradigm to assess spinal learning we observed that mice fed a diet containing DHA/Cur performed better in the spinal learning paradigm than mice fed a diet deficient in DHA/Cur. The enhanced performance was accompanied by increases in the mRNA levels of molecular markers of learning, i.e., BDNF, CREB, CaMKII, and syntaxin 3. Concurrent exposure to exercise was complementary to the dietary treatment effects on spinal learning. The diet containing DHA/Cur resulted in higher levels of DHA and lower levels of omega-6 fatty acid arachidonic acid (AA) in the spinal cord than the diet deficient in DHA/Cur. The level of spinal learning was inversely related to the ratio of AA:DHA. These results emphasize the capacity of select dietary factors and exercise to foster spinal cord learning. Given the non-invasiveness and safety of the modulation of diet and exercise, these interventions should be considered in light of their potential to enhance relearning of sensorimotor tasks during rehabilitative training paradigms after a spinal cord injury

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats

Background: Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. Methods: We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1–100 Hz and 1–10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. Results: In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Conclusions: Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles