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J D Steeves

Publications and source records attributed to J D Steeves.

At least 37 records · Page 2Linked to original sources
PubMed1998

Engines, accelerators, and brakes on functional spinal cord repair.

It is proposed that four essential goals should be met for functional repair after traumatic injury of the adult spinal cord. These include protecting neural tissue after injury and limiting secondary cell damage; replacing lost tissue with transplanted cell "bridges"; blocking the expression of intrinsic factors within the adult CNS that inhibit neural repair; and providing appropriate sensorimotor activity to enhance plasticity within surviving circuits, as well as consolidate any anatomical repair/regeneration. Included is a brief discussion on the approaches and limitations in the evaluation of functional spinal cord repair.

Animals↗
PubMed1998

Regeneration of brainstem-spinal axons after lesion and immunological disruption of myelin in adult rat.

We previously observed that the transient developmental suppression of myelination or disruption of mature myelin, by local intraspinal infusion of serum complement proteins along with a complement-fixing, myelin-specific antibody (e.g., anti-Galactocerebroside), facilitated avian brainstem-spinal axonal regeneration after spinal transection. We now report the effects of similar immunological protocols on axonal regeneration in the injured adult rat spinal cord. After a lateral hemisection injury of the T10 spinal cord, infusion of the above reagents, over 14 days at T11, facilitated the regeneration of some brainstem-spinal axons. The hemisection lesion enabled comparisons between the retrograde labeling within an injured brainstem-spinal nucleus and the uninjured contralateral homologue. The brainstem-spinal nucleus examined in detail was the red nucleus (RN), chosen for its relatively compact descending pathway within the dorsolateral cord. Comparing the number of labeled neurons within each RN, of an experimentally myelin suppressed animal, indicated that approximately 32% of injured rubrospinal projections had regenerated into the caudal lumbar cord. In contrast, control-treated animals (e.g., PBS vehicle alone, GalC antibody alone, or serum complement alone) showed little or no axonal regeneration. We also examined the ultrastructural appearance of the treated cords. We noted demyelination over 1-2 segments surrounding the infusion site (T11) and a further two segments of myelin disruption (delamination) on either side of the demyelinated zone. The demyelination is an active process (< 3 days) with microglia and/or macrophages engulfing myelin. Thus, the facilitation of axonal regeneration through the transient suppression of CNS myelin may be fundamental to all higher vertebrates.

Animals↗
PubMed1998

Asymmetric bipedal locomotion--an adaptive response to incomplete spinal injury in the chick.

The purpose of this study was to compare the asymmetric gait induced by unilateral spinal cord injury in chicks with asymmetric gaits of other bipeds and quadrupeds. After lateral hemisection of the left thoracic spinal cord, kinetic (ground reaction forces) and kinematic (distance and timing) data were recorded as chicks moved overground unrestrained. Ground reaction forces were analyzed to obtain the mechanical energy changes throughout the stride. Kinematic measurements were obtained over a range of speeds to determine the velocity-dependent characteristics of the gait. Hemisected chicks adopted an asymmetric hopping gait in which the animals hopped from the right leg (contralateral to the lesion) onto the left (ipsilateral) leg but then fell forward onto the right leg. Mechanical energy fluctuations throughout a single stride (i.e., two steps) approximated the oscillations that occur during a single walking step of control animals. When examined over a range of velocities, asymmetries in limb timing remained constant, but distance measurements such as step length became more symmetric as speed increased. The results show that, after spinal hemisection, adaptations of the remaining neural circuitry permitted the production of a locomotor pattern that, in addition to providing effective support and propulsion, incorporated some of the energy-conserving mechanisms of the normal walk. Adjustment of this novel locomotor pattern for different velocities further demonstrates the flexibility of locomotor circuitry. Comparisons with other studies shows that this gait shares some temporal and energetic features with asymmetric gaits of several bipedal species, including humans. In particular, hemisected chicks and some hemiplegic humans adopt an asymmetric gait in which maximum energy recovery occurs during the stance of the affected limb; these similarities probably relate to common mechanical constraints imposed on bipedal forms of terrestrial locomotion.

Animals↗
PubMed1997

Sensorimotor stimulation to improve locomotor recovery after spinal cord injury.

Functional recovery after CNS injury may depend, in part, upon reorganization of undamaged neural pathways. Spinal cord circuits are capable of significant reorganization, in the form of both activity-dependent and injury-induced plasticity. This plasticity is manifest behaviourally in the ability of spinal animals to learn new locomotor tasks. Recent work with spinal-injured humans demonstrates that training can improve functional locomotor abilities. New methodologies to enhance limb movement are designed to exploit further the plastic capabilities of the spinal cord by reinforcing appropriate connections in an activity-dependent manner. In the future, these methods might also prove useful in guiding and strengthening functional synaptogenesis of regenerating axons to maximize their contribution towards restoration of function.

Animals↗
PubMed1997

In vivo immunological suppression of spinal cord myelin development.

The onset of myelination in the embryonic chick spinal cord begins on embryonic day (E) 12 or E13 of the 21 day in ovo developmental period. This event coincides with a loss of functional axonal regeneration following complete transection of the thoracic spinal cord. In this study, we have characterised an immunological method for delaying the developmental onset of myelination in vivo until later stages of development (developmental myelin-suppression). A single injection of heterologous or homologous serum complement proteins plus myelin-specific, complement-binding antibodies into the spinal cord prior to E13 delayed the onset of myelination until E17. The state of spinal cord myelin was assessed with immunohistochemical, histological and ultrastructural techniques. Northern blot analysis indicated that myelin basic protein mRNA was not down-regulated in myelin-suppressed spinal cords, which suggests that oligodendrocytes survived developmental myelin-suppression. Glial fibrillary acidic protein immunostaining of normal and treated tissue indicated that myelin-suppression did not alter the resident astrocyte population of the spinal cord or elicit astrogliosis. Immunostaining with microtubule-associated protein-2 and thionine staining of normal and myelin-suppressed tissue further indicated that the neuronal architecture was unaffected by the immunological protocol.

Animals↗
PubMed1996

Ontogeny of bipedal locomotion: walking and running in the chick.

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.

Animals↗
PubMed1995

Phasic cutaneous input facilitates locomotor recovery after incomplete spinal injury in the chick.

1. Walking and swimming of hatchling chicks was videotaped before hemisection of the left thoracic cord and thereafter at regular intervals, for up to 2 wk. With the use of kinematic techniques, movements of the left knee and ankle were quantified to assess recovery of the ipsilateral leg during walking and swimming trials. To study the effects of exteroceptive (cutaneous) feedback in the absence of limb loading, one group of animals was also provided with cutaneous stimulation during swimming in the form of neutrally buoyant tubes that only contacted the foot during the retraction (extension) phase of the swim cycle. 2. One day after hemisection, for both swimming and walking, the left knee failed to extend normally, and the ankle joint remained hyperextended. During walking, all chicks adopted an asymmetric gait, whereas during swimming the left leg remained retracted and motionless. 3. Over the next 2 wk, knee extension and ankle flexion during walking recovered to normal preoperative values, but neither measure returned to preoperative values during swimming trials. However, when chicks were provided with phasic cutaneous stimulation during swimming trials, they showed improvements in leg motion as soon as 5 days after hemisection. Temporary removal of the cutaneous stimulation during swimming (5 days after hemisection) resulted in reduced limb action. However, 14 days after hemisection, the improvement in limb motion was retained even when the cutaneous stimulation was not provided. 4. Improvement in leg motion after swim training with phasic cutaneous stimulation took the form of increased extension of the limb during retraction. Possible neurophysiological mechanisms for this behavior include reflex reinforcement of limb extensor activity in response to cutaneous stimulation of the foot. Repeated exposure to phasic stimulation during swimming trials results in a permanent alteration in limb action. Thus increased cutaneous afferent inputs, even in the absence of limb loading, can facilitate locomotor recovery after spinal cord injury.

Animals↗
PubMed1995

Morphometric abnormalities in brains of great blue heron hatchlings exposed in the wild to PCDDs.

Great blue heron hatchlings from colonies in the Strait of Georgia, British Columbia, Canada are being monitored for environmental contaminant exposure and effects by the Canadian Wildlife Service. The contaminants of concern are polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), primarily derived from kraft pulp mill effluent. The levels of PCDDs and PCDFs in eggs from the most contaminated colonies peaked in 1988 and 1989 and dropped dramatically through 1990 to 1992. Brains of heron hatchlings (taken as eggs from the wild and hatched in the laboratory) were analyzed for gross morphological abnormalities. Brains from highly contaminated colonies (Crofton, British Columbia and University of British Columbia Endowment Lands) in 1988 exhibited a high frequency of intercerebral asymmetry. The frequency of this abnormality decreased in subsequent years as the levels of TCDD and TCDD-TEQs (toxic equivalence factors) decreased. The asymmetry was significantly correlated with the level of TCDD and TCDD-TEQs in eggs taken from the same nest. Yolk-free body weight negatively correlated and the brain somatic index positively correlated with the TCDD level in such pair-matched eggs. These results indicate that gross brain morphology, and specifically intercerebral asymmetry, may be useful as a biomarker for the developmental neurotoxic effects of PCDDs and related chemicals.

Abnormalities, Drug-Induced↗
PubMed1995

Axonal regeneration and physiological activity following transection and immunological disruption of myelin within the hatchling chick spinal cord.

Transections of the chicken spinal cord after the developmental onset of myelination at embryonic day (E) 13 results in little or no functional regeneration. However, intraspinal injection of serum complement proteins with complement-binding GalC or 04 antibodies between E9-E12 results in a delay of the onset of myelination until E17. A subsequent transection of the spinal cord as late as E15 (i.e., during the normal restrictive period for repair) results in neuroanatomical regeneration and functional recovery. Utilizing a similar immunological protocol, we evoked a transient alteration of myelin structure in the posthatching (P) chicken spinal cord, characterized by widespread "unravelling" of myelin sheaths and a loss of MBP immunoreactivity (myelin disruption). Myelin repair began within 7 d of cessation of the myelin disruption protocol. Long term disruption of thoracic spinal cord myelin was initiated after a P2-P10 thoracic transection and maintained for > 14 d by intra-spinal infusion of serum complement proteins plus complement-binding GalC or 04 antibodies. Fourteen to 28 d later, retrograde tract tracing experiments, including double-labeling protocols, indicated that approximately 6-19% of the brainstem-spinal projections had regenerated across the transection site to lumbar levels. Even though voluntary locomotion was not observed after recovery, focal electrical stimulation of identified brainstem locomotor regions evoked peripheral nerve activity in paralyzed preparations, as well as leg muscle activity patterns typical of stepping in unparalyzed animals. This indicated that a transient alteration of myelin structure in the injured adult avian spinal cord facilitated brainstem-spinal axonal regrowth resulting in functional synaptogenesis with target neurons.

Animals↗
PubMed1994

Molecular correlates of spinal cord repair in the embryonic chick: heparan sulfate and chondroitin sulfate proteoglycans.

Proteoglycan (PG) biosynthesis in vivo and PG-associated neurite growth-promoting activity in vitro were examined in the thoracic spinal cord of embryonic chick at times during which functional recovery following axonal damage is permitted, and at later times when such functional recovery is restricted. Over a 10-day period encompassing the permissive and restrictive periods the ratio of newly synthesized heparan sulfate (HS) PG to chondroitin sulfate (CS) PG decreased by more than 50%. Specific PG-associated neurite-promoting activity (NPA) of a PG fraction immobilized on a laminin substrate was 75-fold higher at E9 than at E17. Perturbations of the two families of PGs indicated that all laminin-bound NPA was associated with HSPGs from E9 cord, and that removal of the influence of CSPGs from PG extracts of E17 cord unmasked neurite-promoting activity on a poly-D-lysine substrate of the same magnitude as that observed on a laminin substrate. Neurite-promoting activity associated with HSPGs and high HS to CS ratios of newly synthesized PGs characterize the permissive period for axonal regeneration in the chick embryo spinal cord. In the restrictive period for axonal regeneration neurite promoting activity is masked by the presence of CSPGs which are synthesized at higher levels than HSPGs.

Animals↗
PubMed1993

Changes in protein expression associated with the developmental transition from permissive to restrictive states of spinal cord repair in embryonic chick.

In this study we examined protein changes accompanying a developmental loss of axon regeneration in the spinal cord occurring around embryonic day 13 (E13) of spinal cord development in the chick. We employed high resolution two-dimensional (2D) gel electrophoresis to identify proteins consistently altering their expression around this critical period. Spinal cord protein fractions were isolated from E8, E10, E12, E14, E16, E18 and post-hatching day 2 spinal cord and separately run on a high resolution 2D gel system. Protein spots were visualized with silver staining and subsequently analyzed. Ten proteins were identified, termed developmental spinal cord proteins (DSPs), with five increasing and five decreasing their abundance over the developmental period studied. Apparent molecular weight and isoelectric points have been calculated and are reported. Further studies, currently underway, will be required to determine if these identified proteins are involved in the developmental loss of regenerative ability.

Amino Acid Sequence↗
PubMed1993

Developmental transition by spinal cord plasma membranes of embryonic chick from permissive to restrictive substrates for the morphological differentiation of neuroblastoma x glioma hybrid NG108-15 cell.

Recent studies of spinal cord development and plasticity, in chick, have demonstrated a loss of regenerative ability correlating to embryonic day (E) 13 of the 21-day developmental period. Here we describe membrane fractions from embryonic chick spinal cords as permissive or restrictive substrates for the neuron-like differentiation of neuroblastoma x glioma hybrid NG108-15 cells, in vitro. Plasma membranes were purified from the thoracic spinal cord of embryos at a series of developmental stages (E10-E18). Micro-well plates were coated with the fractions and NG108-15 cells cultured thereon. Cells adhered to the E10-coated wells and began to differentiate after 2 h, becoming highly differentiated, with neurites 2-3 times longer than the diameter of the cell body after 24 h in in culture. In contrast, cells cultured in E18-coated wells remained as clusters of undifferentiated cells of rounded morphology, even after 48 h in culture. As well, the permissive and restrictive plasma membranes were assessed semiquantitatively as the number of adhering cells after 20 h of culture. Adhesion of cells to the substrate decreased as the embryonic age of the plasma membrane substrate increased. Examination of the plasma membrane fractions, using SDS-PAGE, revealed several proteins in the 40-60 kDa range that varied substantially between E12, E14 and E18. Results of this study provide in vitro confirmation of previous in vivo findings; namely, that early embryonic spinal cord is initially permissive for neuritic outgrowth becoming restrictive around E13.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Axonal regeneration contributes to repair of injured brainstem-spinal neurons in embryonic chick.

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.

Animals↗
PubMed1992

Suppression of the onset of myelination extends the permissive period for the functional repair of embryonic spinal cord.

In an embryonic chicken, transection of the thoracic spinal cord prior to embryonic day (E) 13 (of the 21-day developmental period) results in complete neuroanatomical repair and functional locomotor recovery. Conversely, repair rapidly diminishes following a transection on E13-E14 and is nonexistent after an E15 transection. The myelination of fiber tracts within the spinal cord also begins on E13, coincident with the transition from permissive to restrictive repair periods. The onset of myelination can be delayed (dysmyelination) until later in development by the direct injection into the thoracic cord on E9-E12 of a monoclonal antibody to galactocerebroside, plus homologous complement. In such a dysmyelinated embryo, a subsequent transection of the thoracic cord as late as E15 resulted in complete neuroanatomical repair and functional recovery (i.e., extended the permissive period for repair).

Age Factors↗
PubMed1992

Coordination of wingbeat and respiration in the Canada goose. I. Passive wing flapping.

The effects of passive wing flapping on respiratory pattern were examined in decerebrate Canada geese. The birds were suspended dorsally with two spine clamps while the extended wings were continuously moved up and down with a device designed to reproduce actual wing flapping. Passive wing motion entrained respiration over limited ranges by both increasing and decreasing the respiratory period relative to rest. All ratios of wingbeat frequency to respiratory frequency seen during free flight (Soc. Neurosci. Abstr. 15: 391, 1989) were produced during passive wing flapping. In addition, the phase relationship between wingbeat frequency and respiratory frequency, inspiration starting near the peak of wing upstroke, was similar to that seen during free flight and was unaffected by perturbations of the wing-flapping cycle. Removal of all afferent activity from the wings did not affect the ability of continuous passive wing movement to entrain respiration. However, feedback from the wings was required to produce rapid within-breath shifts in the respiratory period in response to single wing flaps. In conclusion, although feedback from the chest wall/lung may be more important in producing entrainment during the stable conditions of passive wing flapping, wing-related feedback may be critically involved in mediating the rapid adjustments in respiratory pattern required to maintain coordination between wing and respiratory movements during free flight.

Afferent Pathways↗
PubMed1992

Coordination of wingbeat and respiration in birds. II. "Fictive" flight.

To determine whether an interaction between central respiratory and locomotor networks may be involved in the observed coordination of wingbeat and respiratory rhythms during free flight in birds, we examined the relationship between wingbeat and respiratory activity in decerebrate Canada geese and Pekin ducks before and after paralysis. Locomotor activity was induced through electrical stimulation of brain stem locomotor regions. Respiratory frequency (fv) was monitored via pneumotachography and intercostal electromyogram recordings before paralysis and via intercostal and cranial nerve IX electroneurogram recordings after paralysis. Wingbeat frequency (fW) was monitored using pectoralis major electromyogram recordings before, and electroneurogram recordings after, paralysis. Respiratory and cardiovascular responses of decerebrate birds during active (nonparalyzed) and "fictive" (paralyzed) wing activity were qualitatively similar to those of a variety of vertebrate species to exercise. As seen during free flight, wingbeat and respiratory rhythms were always coordinated during electrically induced wing activity. Before paralysis during active wing flapping, coupling ratios (fW/fv) of 1:1, 2:1, 3:1, and 4:1 (wingbeats per breath) were observed. After paralysis, fW and fv remained coupled; however, 1:1 coordination predominated. All animals tested (n = 9) showed 1:1 coordination. Two animals also showed brief periods of 2:1 coupling. It is clear that locomotor and respiratory networks interact on a central level to produce a synchronized output. The observation that the coordination between fW and fv differs in paralyzed and nonparalyzed birds suggests that peripheral feedback is involved in the modulation of a centrally derived coordination.

Animals↗