Spinal injury disrupts connections between the brain and spinal cord, causing life-long paralysis. Most spinal injuries are incomplete, leaving spared neural pathways to motor neurons that initiate and coordinate movement. One therapeutic strategy to induce functional motor recovery is to harness plasticity in these spared neural pathways. Chronic intermittent hypoxia (CIH) (72 episodes per night, 7 nights) increases synaptic strength in crossed spinal synaptic pathways to phrenic motoneurons below a C2 spinal hemisection. However, CIH also causes morbidity (e.g., high blood pressure, hippocampal apoptosis), rendering it unsuitable as a therapeutic approach to chronic spinal injury. Less severe protocols of repetitive acute intermittent hypoxia may elicit plasticity without associated morbidity. Here we demonstrate that daily acute intermittent hypoxia (dAIH; 10 episodes per day, 7 d) induces motor plasticity in respiratory and nonrespiratory motor behaviors without evidence for associated morbidity. dAIH induces plasticity in spared, spinal pathways to respiratory and nonrespiratory motor neurons, improving respiratory and nonrespiratory (forelimb) motor function in rats with chronic cervical injuries. Functional improvements were persistent and were mirrored by neurochemical changes in proteins that contribute to respiratory motor plasticity after intermittent hypoxia (BDNF and TrkB) within both respiratory and nonrespiratory motor nuclei. Collectively, these studies demonstrate that repetitive acute intermittent hypoxia may be an effective and non-invasive means of improving function in multiple motor systems after chronic spinal injury.

1. The purpose of this study was to determine whether the production of an energy-efficient bipedal walk is an innate attribute of a precocial bird. 2. The locomotor characteristics of hatchling chicks were quantified using kinetic (ground reaction forces) and kinematic (stride length, leg support duration) measurements as the animals moved overground unrestrained. All measurements were made over a range of velocities and at regular intervals throughout the first 2 weeks of life. 3. Ground reaction force records showed that, like all terrestrial walking vertebrates, chicks undergo cyclical increases and decreases in the body's potential and kinetic energy with each step. The out-of-phase exchange of potential with kinetic energy is an efficient mechanism for the conservation of energy during walking. However, comparisons between chicks at posthatching (P) days 1-2 and P14 revealed that P1-2 chicks are unable to conserve energy because they walk with disproportionately small potential energy oscillations. During running, however, the oscillations between potential and kinetic energy are similar for both P1-2 and P14 animals. 4. P1-2 chicks also walk with a shorter stride length than P14 chicks. Examination of limb support durations shows that younger animals (P1-2, P3) spend less time in single limb support than P14 animals during walking but not running. 5. The results show that even highly precocial bipeds need to acquire the ability to walk in a controlled and energy efficient manner, although they can innately run as well as an adult. This disparity could be due to the distinct actions of the legs in these two behaviours, and the requirement for longer durations of single leg support during walking. These differences relate to constraints inherent to bipedal locomotion and many of the locomotor changes occurring in the first weeks after hatching may therefore be analogous to similar changes seen during human locomotor development.All terrestrial walking vertebrates, including humans, use different gaits to locomote at different speeds. It has been shown that animals change gaits in order to minimize energy requirements (Hoyt & Taylor, 1981). Studies which evaluate the mechanical work of overground locomotion have defined walking and running in terms of energy exchange (Cavagna, Heglund & Taylor, 1977;Heglund, Cavagna & Taylor, 1982). During locomotion at a constant average speed, the body's centre of mass rises and falls, decelerating and accelerating with each step (Heglund et al. 1982). Walking gaits are energetically efficient because there is an alternating transfer between the potential and kinetic energy of the body within each stride. During walking, the leg acts as a solid strut, so that the body's centre of mass rises over the leg to reach a maximum in the middle of the stance phase, while the opposite leg is swinging forward.Potential energy of the body is therefore greatest during mid-stance. However, the forward velocity of the body is lowest at this point and therefore kinetic energy is at a mini...

In an embryonic chicken, traneto of the thoracic spinal cord prior to embryonic day (E) The anatomical development and functional organization of avian descending brainstem-spinal pathways concerned with locomotion is similar to that of other vertebrates, including mammals (1,(5)(6)(7)(8)(9)(10). If the thoracic spinal cord of an embryonic chicken is transected prior to day 13 (E13) of the 21-day developmental period, the animal will subsequently effect complete neuroanatomical and physiological repair resulting in total functional recovery (8-10). Most importantly, regeneration of previously severed axonal fibers contributes to this repair process (10

Recent results have demonstrated complete anatomical and functional repair of descending brainstem-spinal projections in chicken embryos that underwent thoracic spinal cord transection prior to embryonic day 13 (E13) of the 21 d developmental period. To determine to what extent axonal regeneration was contributing to this repair process, we conducted experiments using a double retrograde tract-tracing protocol. On E8-E13, the upper lumbar spinal cord was injected with the first fluorescent tracing dye to label those brainstem-spinal neurons projecting to the lumbar cord at that time. One to two days later (on E10-E15), the upper to mid-thoracic spinal cord was completely transected. After an additional 7-8 d, a different second fluorescent tracing dye was injected into the lumbar cord at least 5 mm caudal to the site of transection. Finally, 2 d later on E19 to postnatal day 4, the CNS was fixed and sectioned. Brainstem and spinal cord tissue sections were then viewed with epifluorescence microscopy. In comparison to nontrasected control animals, our findings indicated that there were relatively normal numbers of double-labeled brainstem-spinal neurons after a transection prior to E13, whereas the number of double-labeled and second-labeled brainstem-spinal neurons decreases after an E13-E15 transection. In addition, at each subsequent stage of development from E10 to E12, there was a greater number of double-labeled brainstem-spinal neurons (indicating regeneration of previously severed axons) than cell bodies labeled with the second fluorescent tracer alone (indicating subsequent development of late brainstem-spinal projections). Assessment of voluntary open-field locomotion (hatchling chicks) and/or brainstem-evoked locomotion (embryonic or hatchling) indicated that functional recovery of animals transected prior to E13 was indistinguishable from that observed in control chicks (sham operated or unoperated). Taken together, these data suggest that regeneration of previously axotomized fibers contributes to the observed anatomical and functional recovery after an embryonic spinal cord transection.

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