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Biomedical subjects

A R Blight

Publications and source records attributed to A R Blight.

At least 55 records · Page 3Linked to original sources
PubMed1990

Functional recovery after spinal cord hemisection in guinea pigs: the effects of applied electric fields.

Right lateral hemisection of the lower thoracic spinal cord was performed in 216 adult guinea pigs. Animals that proved suitable for the study were divided into one control and two experimental groups. Experimental animals were implanted with intraperitoneal stimulators delivering regulated current of 35 or 50 microA through electrodes placed 1 cm rostral and caudal of the hemisection. The cathode was cranial to the lesion in one group (n = 67) and caudal in the other (n = 33). Control animals (n = 62) were implanted with sham stimulators and electrodes delivering no current. The functional status of the animals was measured by tactile stimulation of the back skin to elicit the cutaneus trunci muscle reflex, and by the vestibulospinal free-fall response. The cutaneous response ipsilateral and caudal to the lesion was lost following hemisection and did not recover in any of the control animals or in animals with cathode caudal to the lesion. Recovery of the response was found in 9 of 67 animals in the cathode rostral group, between 56 and 139 days after injury. Toe spreading recovered spontaneously in 80-90% of animals in all groups. Of the possible mechanisms of skin reflex recovery, most current evidence points to regrowth of ascending nerve fibers in the lateral funiculus of the spinal cord local to the lesion.

Animals↗
PubMed1989

Central axons in injured cat spinal cord recover electrophysiological function following remyelination by Schwann cells.

Axonal morphometry of the lesion site was studied at 3 months after standardized weight-drop contusion injury of the thoracic spinal cord in adult cats. From a sample of 25 injured animals, 12 examples were found in which all surviving axons in the dorsal column were remyelinated by Schwann cells, at the level of the lesion. The dorsolateral tracts were also peripherally myelinated in 6 of these cases, and there was no central myelination in complete transverse sections through the lesion in four animals. In these cases, Schwann cell myelination was prevalent for several millimeters on either side of the lesion center. The extent of Schwann cell invasion correlated with the intensity of injury, measured by overall axon loss. Cortical somatosensory evoked potentials (CSEP) were recorded from all animals before and at intervals for 12 weeks after injury. CSEP to hindlimb (tibial nerve) stimulation were lost immediately at injury but some recovery took place during the first month. The extent of CSEP recovery correlated negatively but weakly with overall axon loss. Clear SEP were recorded at 3 months post-injury in 3 of the animals in which the dorsal columns were remyelinated by Schwann cells; in one of these, the dorsolateral funiculi were also peripherally myelinated. In another, oligodendrocyte myelination was absent from the entire transverse section of the lesion site. Thus, abnormal remyelination by cells of the peripheral nervous system, which is known to occur in a variety of central demyelinating conditions, is capable of restoring effective action potential conduction in mammalian spinal cord sensory tracts.

Animals↗
PubMed1989

Effect of 4-aminopyridine on axonal conduction-block in chronic spinal cord injury.

The spinal cords of 18 anesthetized cats were injured by standardized contusion. The animals were maintained for 4-16 months, then the thoracic spinal cord was isolated in vitro at 25 degrees C. Microelectrode recordings were made from single axons conducting through the lesion in ventral and lateral tracts. On warming the tissue, action potential conduction was found to block at temperatures below 36 degrees C in 29% of 129 axons tested. Of 17 axons in which it was possible to demonstrate a block below physiological temperature, apply 0.1-1 mM 4-AP, wait for 10 min and test conduction again, 7 showed increases in blocking temperature and 4 of these restored to conduction above 37 degrees C. The other 10 fibers showed no improvement in blocking temperature. 4-AP also increased the spontaneous activity of axons. It was concluded that 4-AP may eventually be useful in chronic spinal cord injuries, because it improves safety factor in some axons and increases excitability in others, which may compensate to some extent for the reduction in density of projections through the lesion.

4-Aminopyridine↗
PubMed1987

Behavioral recovery induced by applied electric fields after spinal cord hemisection in guinea pig.

Applied electric fields were used to promote axonal regeneration in spinal cords of adult guinea pigs. A propriospinal intersegmental reflex (the cutaneous trunci muscle reflex) was used to test lateral tract function after hemisection of the thoracic spinal cord. An electrical field (200 microvolts per millimeter, cathode rostral) applied across the lesion led to functional recovery of the cutaneous trunci muscle reflex in 25 percent of experimental animals, whereas the functional deficit remained in control animals, which were implanted with inactive stimulators.

Animals↗
PubMed1987

Augmentation by 4-aminopyridine of vestibulospinal free fall responses in chronic spinal-injured cats.

This study examines the effect of the potassium channel blocker 4-aminopyridine (4-AP) on free fall responses (FFR) in the hindlimb muscles of chronically spinal injured cats. The thoracic spinal cord of 7 adult female cats was injured by a standardized contusion method. At 3-7 months post-injury the FFR in 6 hindlimb muscles was recorded electromyographically in each animal, under ketamine sedation. The normal short-latency response to a sudden drop was severely attenuated in all injured animals and practically undetectable in 2 cases. Within 15 min following intravenous administration of 1 mg/kg 4-AP, there was profound augmentation of the amplitude of the FFR and a tendency toward normalization of latency in all animals, though the normal amplitude range was not attained. The same 4-AP dose produced a relatively small increase of FFR amplitude in only 2 of 4 normal, uninjured animals tested. The data are consistent with previous observations that low doses of 4-AP restore conduction in some critically demyelinated axons, and provide support for the hypothesis that conduction block in surviving axons is responsible for a proportion of the dysfunction in chronic spinal injury. Augmentation of FFR in injured animals may also result partly from increased transmitter release in both spinal cord and periphery, due to the presynaptic effects of 4-AP.

4-Aminopyridine↗
PubMed1987

Failure of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to inhibit cell-cell coupling in newborn mouse epidermal cells and Chinese hamster V79 cells under non-standard culture conditions.

The function of the skin tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) during two-stage carcinogenesis in mice remains obscure because of TPA's numerous phenotypic effects. In vitro studies under established conditions have generated substantial interest in TPA's ability to inhibit, although transiently in some cases, direct cell-cell coupling in several permanent cell lines, by analogy allowing latent 'initiated cells' to escape homeostatic controls in vivo. Using different culture conditions designed to improve the growth of newborn mouse epidermal cells, we examined dye coupling in these cells, and metabolic co-operation in V79 cells, finding no effect of TPA on coupling. It appears that this effect of TPA is overly sensitive to in vitro conditions. Since a corresponding physiological effect has not yet been demonstrated in vivo, future studies should be directed to establish that coupling inhibition by TPA actually does occur and plays some role during tumor promotion in vivo, and is not merely a characteristic of certain culture systems.

Animals↗
PubMed1986

Axonal regeneration in spinal cord injury: a perspective and new technique.

A set of techniques is described for determining the response of mammalian spinal axons to transection. The logical selection and the advantages of these techniques are discussed. The dorsal column of guinea pig thoracic spinal cord was transected with a tungsten needle and the position of the lesion was marked by a staple-shaped wire device (Foerster: J. Comp. Neurol. 210:335-356, '82). The morphology of dorsal column axons projecting rostrally toward the lesion was examined between 1 and 50 days postlesion by anterograde staining with horseradish peroxidase, applied to a second lesion of the dorsal column two to three vertebral segments caudal to the first. Axons damaged by the original lesion were found to die back 1-2 mm from the plane of transection and at 18-20 hours were characterized by terminal club-shaped swellings attached to the proximal axon by a thin connection. At 50 days postlesion there was some evidence of limited regenerative responses in terms of growth-cone-like axon terminals, and the presence of aberrant axonal branching, but no evidence of regenerating axons approaching close to the plane of transection. These findings are in agreement with previous studies indicating little or no effective regrowth of myelinated axons in the mammalian spinal cord. These same techniques were used in a succeeding study to examine the effects of applied electric fields on the axonal response to transection.

Animals↗
PubMed1986

Transected dorsal column axons within the guinea pig spinal cord regenerate in the presence of an applied electric field.

Using an implanted battery and electrodes, we have imposed a weak, steady electrical field across partially severed guinea pig spinal cords. We have analyzed regeneration of dorsal column axons in experimental animals and sham-treated controls at 50-60 days postinjury by anterograde filling of these axons with the intracellular marker horseradish peroxidase and by employing a marking device to identify precisely the original plane of transection (J. Comp. Neurol. 250: 157-167, '86). In response to electric field applications, axons grew into the glial scar, as far as the plane of transection in most experimental animals. In a few animals axons could be traced around the margins of the lesion (but never through it). Moreover, these fibers returned to their approximate positions within the rostral spinal cord before turning toward the brain. In sham-treated controls, ascending axons were found to terminate caudal to the glial scar, and rarely were any fibers found within the scar itself. Axons were never observed to cross into the rostral cord segment. These findings suggest that an imposed electrical field promotes growth of axons within the partially severed mammalian spinal cord, that a steady voltage gradient may be an environmental component necessary for axonal development and regeneration, and that some component(s) of the scar impede or deflect axonal growth and projection.

Animals↗
PubMed1986

Morphometric analysis of experimental spinal cord injury in the cat: the relation of injury intensity to survival of myelinated axons.

The pattern of axonal destruction and demyelination that occurs in experimental contusion injury of cat thoracic spinal cord was studied by line sampling of axons in 1 micron thick plastic sections with the light microscope. Injuries were produced by a weight-drop apparatus, with the vertebral body (T9) below the impact stabilized by supports under the transverse processes. The effects of two combinations of weight and height were examined: 10 or 13 g dropped 20 cm onto an impact area of 5 mm diameter. Animals were kept for 3-5 months after injury, then fixed by perfusion for histological analysis. The number of surviving myelinated axons was found to vary both with the weight used and with the size of the spinal cord. A measure of impact intensity was derived from the calculated momentum of the weight at impact divided by the cross sectional area of the cord (interpolated from dimensions measured rostral and caudal of the lesion following fixation). At impact intensities greater than 0.02 kg-m/s/cm2 there was practically no survival of axons at the center of the injury site, combined with almost complete breakdown of the pial margin. Between 0.08 and 0.2 kg-m/s/cm2 the number of surviving axons varied between 100,000 and 2,000, approximating a negative exponential function (r = -0.88). The number of axons surviving in the outer 100 microns of the cord varied practically linearly (r = -0.82) between near normal and less than 1% of normal over the same range of injury intensity. The number of surviving axons decreased with depth from the pia, also approximating a negative exponential function, with a 10-fold decrease in density over approximately 500 microns. The average slope of this relation with depth remained similar over the range of injury intensity examined, though the slope appeared inversely related to variation in axonal survival for different individuals at a given intensity. It is argued that the loss of axons is probably determined primarily by mechanical stretch at the time of impact. Its centrifugal pattern may be explained by longitudinal displacement of the central contents of the cord, reflecting the viscoelastic "boundary layer" properties of parenchymal flow within the meningeal tube. This is illustrated with reference to the behavior of a gelatin model under compression. The preferential loss of large caliber axons and the characteristic shift to abnormally thin myelin sheaths (resulting from post-traumatic demyelination) both varied in extent independently of injury intensity and overall axonal survival.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Motor evoked potentials in CNS trauma.

The evolving techniques of motor evoked potential (MEP) monitoring are reviewed here with reference to their application in clinical and experimental CNS trauma, and with particular relevance to spinal cord injury. Transcutaneous electrical stimulation of the motor cortex for analysis of descending pathways has been developed over the past 6 years in a number of centers. It has now been greatly augmented by the introduction of magnetic stimulation technology. The MEP offers a valuable insight into the physiological status of motor tracts within the spinal cord and is applicable to conscious patients, intraoperative monitoring, and animal studies. It is seen as complementary to somatosensory evoked potential monitoring rather than an alternative or replacement for it. The chief limitations of the technique, common to all evoked potential methods, are the restricted information content, and the need for rigorous electrophysiological interpretation of the resulting signals, if meaningful diagnostic data are to be extracted.

Animals↗
PubMed1985

Depolarizing afterpotentials in myelinated axons of mammalian spinal cord.

Microelectrode recordings were made from 5-10 micron dia axons of adult rat spinal cord in vitro. Action potentials in response to electrical stimulation were recorded intracellularly and electrical characteristics of the axons were examined by injecting current pulses through a bridge circuit. All action potentials larger in amplitude than 80 mV were followed by depolarizing afterpotentials, similar to those recorded in peripheral axons [Barrett and Barrett (1982) J. Physiol., Lond. 323, 117-144]. The afterpotential could be described as the sum of three exponential components, the time constants of which (tau 1, tau 2 and tau 3) were 25.2 +/- 5.6, 3.1 +/- 0.8 and 0.8 +/0 0.3 ms, respectively, at 25 degrees C and a membrane potential of -80 mV. The maximal amplitudes of the afterpotential components, obtained by extrapolating to the peak of the action potential, were 3.8 +/- 1.0, 6.4 +/- 5.2 and 21.7 +/- 9.8 mV, for action potential amplitudes of 102 +/- 11 mV. The amplitude of the longest component of the afterpotential decreased with depolarization and increased with hyperpolarization at the recording site. The amplitude decreased markedly with increase of temperature to physiological levels, in conjunction with the expected decrease in action potential duration. Similar afterpotential components were present in the response of the axon to injected hyperpolarizing current pulses. The observations are consistent with the suggestion [Barrett and Barrett (1982) J. Physiol., Lond. 323, 117-144] that the afterpotential results from charging of the axolemmal capacitance by current passing through the myelin sheath during the action potential. They are inconsistent with a number of calculations of electrical characteristics of peripheral axons derived from voltage clamp experiments in isolated fibers. It is argued that the electrical resistance of the myelin lamellae is relatively low, though within the range calculated for other glial membranes. This suggestion is found more compatible with the available morphological data than the alternative proposal that a leakage pathway under the myelin sheath might be responsible for the afterpotential [Barrett and Barrett (1982) J. Physiol., Lond. 323, 117-144]. The significance of this organization for the function of myelinated axons and the electrical basis of the afterpotential are examined further in the accompanying paper [Blight (1985) Neuroscience 15, 13-31].

Action Potentials↗
PubMed1985

Computer simulation of action potentials and afterpotentials in mammalian myelinated axons: the case for a lower resistance myelin sheath.

Depolarizing afterpotentials, recorded in peripheral nerves [Barrett and Barrett (1982) J. Physiol., Lond. 323, 117-144] and spinal axons [Blight and Someya (1985) Neuroscience 15, 1-12], have been interpreted as representing passive discharge of axolemmal capacitance. This interpretation requires a lower resistance pathway through the myelin sheath than previous measurements have suggested. A computer model was used to examine the contribution of the electrical characteristics of nerve fibers to action potential conduction and afterpotential generation. The model consisted of a resistance-capacitance network representing a chain of 20 internodes. The resistances of node, internode and myelin sheath, deduced from observations in the accompanying paper, [Blight and Someya (1985) Neuroscience, 15] were found to produce suitable length and time constants, and prolonged afterpotentials, when inserted into the model. Similar length and time constants were found using a conventional model of the axon, based on measurements from isolated peripheral fibers, but this did not reproduce the afterpotentials. Action-potential conduction velocity is enhanced by reducing the time constant and increasing the length constant. The problem of minimizing the internodal time constant was met in the conventional model through the low parallel resistance of the node, while in the new model it was met by reducing the resistance of the myelin sheath. The latter strategy required the nodal leakage resistance to be higher than values from single fiber measurements (ca 250 M omega rather than ca 50 M omega) in order to maintain the length constant similar to the conventional model. Simulation of the recorded potentials required the resistance of the myelin lamellae to be approx. 100 omega cm2. The model quantitatively reproduced the voltage response of the axon to injected current pulses and to propagated action potentials, using Frankenhaeuser-Huxley kinetics. [Frankenhaeuser and Huxley (1964) J. Physiol., Lond. 171, 302-315; Frankenhaeuser and Moore (1963) J. Physiol., Lond. 169, 431-437]. The short duration components of the afterpotential, observed in mammalian recordings were reproduced by assuming a leakage pathway in the myelin sheath, at the impalement site. The calculated lower resistance of the myelin sheath was such that it minimized the effective internodal time constant for a given nodal resistance. This appears to free the myelinated fiber from the alternative requirement for a high nodal leakage conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Delayed demyelination and macrophage invasion: a candidate for secondary cell damage in spinal cord injury.

Recent studies of the chronic morphology and physiology of experimental spinal cord injury (SCI) in the cat are reviewed and their conclusions outlined. In particular, variations in chronic dysmyelination of the lesion have been found to be largely independent of injury intensity, suggesting a secondary pathologic origin. New morphometric studies of the subacute development of contusion lesions are described. Using electron microscopy and light microscopic line-sampling of myelinated axons, it was found that demyelination of axons that survived the initial injury occurred largely between 2 and 7 days after contusion and did not accompany the much more rapid dissolution of myelin from those axons that degenerated within the first 2 days. The number of apparently intact axons at the center of the lesion declined by a factor of 2 or more in the same interval of 2-7 days. This secondary pathology was coincident with dense invasion of the lesion by macrophages and their phagocytosis of the membraneous debris remaining from the initial hemorrhagic necrosis. It is concluded that posttraumatic inflammation in the spinal cord should be investigated in more detail as a possible contributor to chronic deficits. In addition, these data emphasize the importance of defining the nature, time of occurrence, and proportional significance of secondary damage in order to evaluate those studies and hypotheses that attempt to differentiate acute secondary pathophysiology from primary degenerative processes.

Animals↗
PubMed1983

Axonal physiology of chronic spinal cord injury in the cat: intracellular recording in vitro.

The properties of action potential conduction in single axons of the cat thoracic spinal cord were examined with microelectrode recording and electrical stimulation in vitro. The study included normal animals, animals chronically paralyzed by contusion of the cord, and animals showing some degree of locomotory recovery following a similar injury and several weeks of transient paralysis. The control studies were designed to compare the results of microelectrode sampling in vitro with morphological and in vivo physiological data. The pathophysiological studies were intended to investigate the continuity and function of axons identified morphologically in paralyzing lesions, and to examine the hypothesis that functional loss is associated with chronic axonal dysfunction, as well as direct axonal loss. Most of the recordings were made from dorsal columns and ventral tracts at 23-25 degrees C. The conduction velocities recorded in the normal cord were consistent with morphological data on caliber spectra, given the selectivity of the microelectrodes for larger axons. The refractory period of transmission was approximately 2-4 ms at 23-25 degrees C and 0.7-2 ms at 37 degrees C. Prolonged depolarizing after-potentials were recorded, following action potentials greater than 70 mV amplitude. Axons outside the lesion in injured cord showed only slight reductions from control in the mean and range of conduction velocity and refractory period distributions. The number of axons impaled per electrode track was reduced by up to one half. Relatively few impaled axons conducted through the lesion site in the injured cords: 16% in recovering animals and 7% in chronically paralyzed, as compared with 61% in uninjured controls. The mean conduction velocity of these through-conducting axons was significantly less than that of the normal population, particularly in paralyzed animals, and refractory period was significantly prolonged for conduction through the lesion in the paralyzed group. When axons conducting through the middle of the isolated spinal tract were challenged by raising the temperature, conduction block occurred below physiological temperature (37 degrees C) for 7% of axons in controls, 14% in recovering and 73% in paralyzed cats. The mean temperature of heat block in normal axons was 41 degrees C. Some axons appear to survive in paralyzing contusion trauma of this type. Those axons that remain in the lesion site project through it but their conduction properties are abnormal, particularly in animals that remain chronically paralyzed. Action potentials in many axons may be effectively blocked at the chronic lesion site, contributing to the overall functional d

Animals↗
PubMed1983

Cellular morphology of chronic spinal cord injury in the cat: analysis of myelinated axons by line-sampling.

A systematic line-sampling method is described for counting and mapping myelinated axons in transverse sections of the spinal cord. Its advantages over random sampling of small areas are considered. The technique was applied to quantifying experimental weight-drop contusion injuries of cat spinal cord, from several months to more than a year after injury. Contusion of the mid-thoracic cord with a 20 g weight dropped 20 cm was usually sufficient to produce chronic hindlimb paralysis whilst allowing the survival of significant numbers (40,000-110,000) of myelinated axons passing through the lesion site. The axons which survived were concentrated towards the pial surface. There was a proportionally greater loss of larger diameter axons, but this was independent of distance from the pia, indicating that at least two independent factors contribute to selective axonal death following injury, one related to depth within the cord, the other to axon diameter. Myelin sheath thickness was decreased from normal and this deficit also increased with depth. There was overlap in all these quantitative morphological characteristics between animals showing some recovery of hindlimb locomotion and those with maintained spastic paralysis at more than six months after injury. Effective locomotion was found to recover in some cases with the maintenance of a small proportion (5-10%) of the original axonal population, largely concentrated in a rim only 200-300 microns thick. Morphological correlates of paralysis in chronic injuries included severe reduction of axonal number, selective elimination of large fibers, and sustained dysmyelination. Any one or combination of these may be responsible for chronic paralysis in individual animals.

Animals↗
PubMed1982

Miniature synaptic potentials absent from motoneurons of intact spinal cord.

Intracellular recordings were made from lumbar motoneurons of decerebrate, paralyzed frogs with minimal surgical damage to the spinal cord. Detectable spontaneous synaptic activity was absent in most motoneurons, as compared with published in vitro recordings. Lesions of the thoracic cord increased the incidence of small spontaneously occurring potentials. This suggests that spontaneous quantal release of transmitter observed in isolated preparations is a consequence of presynaptic neuronal damage.

Animals↗
PubMed1982

Miniature endplate potentials related to neuronal injury.

Intracellular recordings were made in vivo from muscle fibers of anesthetized or spinalized frogs. Characteristic 'spontaneous' miniature endplate potentials were rarely recorded in intact muscles by comparison with muscles acutely denervated in the same animals. It is concluded that little or no spontaneous quantal release of transmitter occurs in vivo, in contrast with isolated preparations. The presence effectively 'silent' endplates was confirmed by evoking quantal release with hypertonic saline.

Animals↗