Biomedical subjects

J Rosenbluth

Publications and source records attributed to J Rosenbluth.

At least 37 records · Page 2Linked to original sources

PubMed1990

Myelin formation following transplantation of normal fetal glia into myelin-deficient rat spinal cord.

Structurally normal myelin sheaths develop in the spinal cord of juvenile myelin-deficient rats (mdr) 11 days after transplantation of normal fetal spinal cord fragments or cultured cells that do not yet express galactocerebroside. Cultures result in more extensive myelin formation, and in both cases the myelin that forms is located primarily at or near the site of transplantation. Myelin formation also occurs after transplantation of postnatal donor tissue, but the extent diminishes with donor age, and none was seen after transplantation of adult donor tissue over the two-week period studied. Injection of killed tissue, tissue derived from mouse donors or an extract of myelin also did not lead to myelin formation. The results imply that myelin formed in the host following transplantation was generated by oligodendrocytes newly differentiated from donor precursor cells rather than by donor oligodendrocytes that were already mature at the time of transplantation or by host oligodendrocytes that took up components of the injected material. We conclude that exogenous fetal glial cell precursors are able to survive, differentiate and form myelin in the environment of the juvenile mdr spinal cord.

Aging↗

PubMed1990

Axolemmal abnormalities in myelin mutants.

Evidence is reviewed that the paranodal axoglial junction plays important roles in the differentiation and function of myelinated axons. In myelin-deficient axons, ion flux across the axolemma is greater than that in myelinated fibers because a larger proportion of the axolemma is active during continuous, as opposed to saltatory, conduction. In addition, older myelin-deficient rats that have developed spontaneous seizures display small foci of node-like E-face particle accumulations in CNS axons as well as more diffuse regions of increased particle density and number. Assuming that the E-face particles represent sodium channels, such regions could underlie high sodium current density during activity, low threshold for excitation, and increased extracellular potassium accumulation. Depending on the degree of spontaneous channel opening, they could also represent sites of spontaneous generation of activity. The appearance of seizures and their gradual increase in frequency and severity could represent an increase in the number of such regions. In addition, diminution in the dimensions of the extracellular space during maturation would result in increased extracellular resistance, which, together with increasing axonal diameter, would tend to increase the likelihood of ephaptic interaction among neighboring axons as well as the likelihood of extracellular potassium rises to levels that could cause spontaneous activity.

Animals↗

PubMed1989

Myelin formation in myelin-deficient rat spinal cord following transplantation of normal fetal spinal cord.

Previous studies of the myelin-deficient rat spinal cord have suggested that astrocytes may play a role in preventing the formation of myelin in this mutant, or causing its breakdown. Comparison of mutant and normal littermate spinal cords shows a marked hypertrophy of astrocytes in the mutant in both gray matter and fiber tract regions. Nevertheless, when normal fetal spinal cord fragments are transplanted into mutant host spinal cord, clusters of normal-looking myelin sheaths develop with no sign of attack by host astrocytes.

Animals↗

PubMed1989

Spinal cord lesions block seizures or delay their onset in myelin-deficient rats: evidence that generalized tonic seizures can be triggered by abnormal spinal cord activity.

The myelin-deficient mutant rat develops generalized tonic seizures and dies during the fourth postnatal week. Surgical constriction of the lower thoracic spinal cord, performed either after the seizures have appeared or before, eliminates the seizures, or delays their onset, and prolongs the life of the animals. These observations support the view that the seizures in these animals can be triggered by abnormal activity originating in the myelin-deficient spinal cord and can be blocked by preventing that activity from ascending to higher levels. Similar seizures and "paroxysmal" phenomena occur in other myelin-deficient conditions including multiple sclerosis.

Animals↗

PubMed1989

Extracellular potassium activity and axonal conduction in spinal cord of the myelin-deficient mutant rat.

We recorded somatosensory evoked potentials SEPs), extracellular K+ ionic activity ([K+]e), and K+ clearance rates in the spinal cords of 14 myelin-deficient mutant rats and 16 normal male littermates at 16-41 days after birth. Tested under pentobarbital anesthesia (25 mg/kg ip) and hypothermic conditions (32-34 degrees C), myelin-deficient rats had longer cortical SEP latencies (67 +/- 20 ms) compared to those in normal siblings (48 +/- 15 ms; P less than 0.05). Mean baseline [K+]e levels were 2.6 +/- 0.5 mM in myelin-deficient rats and 2.6 +/- 0.8 mM in normal siblings. Clearance times of KCl solutions injected into the spinal cord were biphasic and exponential. The mean initial and secondary exponential half-times were 1.0 +/- 0.5 and 2.7 +/- 1.7 min for myelin-deficient rats and 0.8 +/- 0.4 and 3.8 +/- 3.2 min for normal siblings. Repetitive sciatic nerve stimulation (2-20 Hz, 2- to 6-s trains) produced 1-3 mM transient [K+]e rises in thoracic and lumbar cords of myelin-deficient rats. The [K+]e rises were largest in the dorsal spinal cord at 200-500 microns depth. The normal siblings had smaller or no stimulus-induced [K+]e rises. In myelin-deficient rats, injection of 1 mM 4-aminopyridine (4-AP) solution into the thoracic spinal cord completely suppressed the stimulus-induced [K+]e and markedly increased spinal and cortical SEP amplitudes for several hours. In the normal siblings, the 4-AP injections transiently blocked spinal conduction for 20-30 min but thereafter enhanced cortical SEP amplitudes for 2-3 h. We conclude that sciatic nerve stimulation produces spinal cord [K+]e rises in myelin-deficient rat larger than those in the normal siblings, that the [K+]e transients represent increased K+ release rather than impaired K+ clearance, and that the K+ ions come from 4-AP blockable sources.

4-Aminopyridine↗

PubMed1988

Nodal and paranodal structural changes in mouse and rat optic nerve during Wallerian degeneration.

Ultrastructural changes in nodal and paranodal regions of myelinated mouse and rat optic nerve fibers were followed between 4 h and 28 days during the course of Wallerian degeneration. In the mouse, axoplasmic changes, including accumulation of organelles and segregation of microtubules, were detectable 4 h after transection, and progressed to a maximum level on day 4, at which time many axons were markedly swollen. Dense axoplasm was seen as early as 16 h and was a common feature of degenerating axoplasm at later times. Paranodal changes, which first appeared as early as 16 h after injury, included detachment of terminal loops of myelin from the axolemma, disconnection of terminal loops from compact myelin lamellae and broadening of terminal loops, or separation of the loops from each other, resulting in paranodal elongation. In freeze-fracture replicas, the E-face of the axolemma showed the normal particle distribution as late as days 3-5. By day 8, however, the nodal particles were patchy and the overall nodal particle density was reduced to approximately half normal. Some normal-looking fibers were present at all stages examined, but their number had declined to about half the total population on day 5 and to less than 10% on day 11. In the rat, the overall sequence of events and time course were comparable to those in the mouse. Thus, the morphological changes found follow approximately the same sequence as that described previously in frog nerves, but progress more rapidly in the mouse and rat.

Animals↗

PubMed1988

Spinal cord injury or spinal anesthesia eliminates seizures in myelin-deficient rats.

The generalized tonic seizures that occur in myelin-deficient rats can be eliminated temporarily by spinal cord injury or spinal anesthesia. These observations imply that the seizures in this mutant can be triggered by activity in the spinal cord. The results are consistent with an earlier proposal that axons in myelin-deficient CNS fiber tracts can interact to produce abnormal excitation.

Anesthesia, Spinal↗

PubMed1988

Freeze-fracture study of the perineurium around frog dorsal root ganglia.

The perineurium around frog dorsal root ganglia consists of layers of flattened cells separated by extracellular connective tissue elements. The number of layers is smaller than that in the perineurium around adjacent peripheral nerves, and some of the layers are discontinuous, but in both cases, cells in the same layer overlap and form tight junctions with each other, sometimes accompanied by desmosomes or gap junctions. In freeze-fracture replicas the tight junctions between perineurial cells around peripheral nerves consist of 13-91 strands (mean: approximately 38). Some of these are parallel to the cell borders and some are oblique, forming elaborate meshworks. The overall width of each junction averages approximately 12 microns. In contrast, the tight junctions between perineurial cells around ganglia are much narrower, averaging approximately 2 microns in width, and they consist of only 1-14 strands (mean: approximately 6) with few anastomoses and many free ends. These structural differences provide a morphological basis for a less complete diffusion barrier around dorsal root ganglia.

Animals↗

PubMed1988

Role of glial cells in the differentiation and function of myelinated axons.

Myelinated axons are highly differentiated in the vicinity of the node of Ranvier, both structurally and with respect to ion channel distribution. Evidence is reviewed showing that axonal differentiation depends upon two distinct types of interaction between glial cells and the axolemma, one at the node itself, with astrocyte processes, and the second, more extensive one, in the paranodal region, with oligodendrocyte processes. In the peripheral nervous system, Schwann cells fulfill both roles. Glial or Schwann cell abnormalities, due to genetic deficiencies, diseases or experimental procedures, result in corresponding abnormalities in the axolemma and can have devastating effects on nerve fiber function. An example, the myelin-deficient mutant rat, is presented, and the defects underlying the profound and ultimately lethal neurological abnormalities seen in this mutant are discussed in relation to abnormalities in its axoglial interactions.

Animals↗

PubMed1987

Nodal and paranodal structure during Wallerian degeneration in frog spinal nerve.

The nodal and paranodal regions of myelinated peripheral nerve fibers in frogs were examined at sequential times (1-24 days) during Wallerian degeneration. In the region up to 3 mm distal to the transection, paranodal demyelination and axoplasmic degeneration became apparent on day 4 and progressed to involve most of the nodes by day 8. The E-fracture face of the axolemma showed a patchy distribution of nodal particles and some paranodal demyelination on days 4 and 6. On day 8, nodal particles were evenly distributed at low concentration and the adjacent demyelinated paranodal regions showed a corresponding increase in particle density, suggesting redistribution of the nodal particles. The sequence of changes seen in comparable to that in Wallerian degeneration of central nervous system (CNS) fibers but progressed more rapidly in the peripheral nervous system (PNS). In addition a higher proportion of PNS fibers shows pathological changes at corresponding time periods.

Animals↗

PubMed1987

Abnormal axoglial junctions in the myelin-deficient rat mutant.

Although the myelin-deficient rat displays a gross deficiency of myelin in the CNS, occasional myelin segments of moderate thickness can be found. The typical lamellar pattern, consisting of alternating major dense and intermediate lines, is present in some regions of such segments, but the pattern is abnormal elsewhere. Redundant folds are common, and astrocyte processes occur frequently between the myelin sheath and axolemma or within the sheath. In the paranodal region, myelin lamellae occasionally form a palisade of 'terminal loops' against the axolemma, but discrete transverse bands occur only rarely and regular arrays of transverse bands over an extended length have not been seen. 'Reversed' paranodal junctions occur more often. Here the outermost layer of myelin, instead of being closest to the node, is furthest from it, and successive layers form terminal loops that approach the node progressively. These loops face away from the axon and do not contact it. At paranodal junctions of this kind only the innermost loop, or a small number of inner loops, adjoins the axolemma and, as a result, the size of the paranodal axoglial junction is markedly restricted. These defects in the paranodal junction may underlie the intrusion of astrocyte processes from either end of a myelin segment into the internodal periaxonal space and between myelin lamellae. Thus, one of the normal functions of the paranodal junction may be to restrict extension of astrocyte processes into and beneath myelin segments. The myelin-deficient rat also exhibits node-like specializations of the axolemma in association with glial cell processes.

Animals↗

PubMed1986

Structure of the satellite cell sheath around the cell body, axon hillock, and initial segment of frog dorsal root ganglion cells.

The structure of the satellite cell sheath of frog dorsal root ganglion cells was studied in thin sections and freeze-fracture replicas. The sheath around the cell body is composed of thin satellite cell lamellae closely applied to the neuronal plasma membrane. At the axon hillock the sheath divides into outer and inner components separated by a broad space containing a distinctive extracellular matrix and occasional flattened satellite cell processes. The sheath around the initial segment is usually multilayered but less compact than that around the cell body, and in some places it exhibits node-like interruptions. Apart from occasional particle groupings characteristic of tight junctions and gap junctions, the satellite cells display homogeneously distributed intramembranous particles in both fracture faces in all regions of the sheath.

Animals↗

PubMed1986

Nodal and paranodal structural changes in frog optic nerve during early Wallerian degeneration.

Ultrastructural changes in the nodal and paranodal regions of myelinated nerve fibres of frog optic nerves were studied during early stages of Wallerian degeneration. The earliest changes seen include retraction of paranodal loops of myelin from the axolemma and disconnection of paranodal myelin loops from myelin lamellae. These paranodal changes are asymmetric around the node and may be more advanced on either the proximal or distal side. Axoplasmic changes, including segregation of microtubules from neurofilaments, disorientation of microtubules and accumulation of abnormal organelles at nodes, appear shortly. In some axons the 'undercoating' along the widened nodal surfaces becomes patchy, and blebs appear in the nodal axolemma. In freeze-fracture replicas a mixture of particle clusters and particle-free areas appears in both E- and P-faces of the nodal axolemma. Blebs remain particle free. Initially, E-face particles remain segregated to the node and are present only at much lower concentrations in the demyelinated paranodal axolemma, suggesting that they are not freely mobile at this stage. Nodal E-face particles begin to decrease on day 5 associated with an increase in particles at the adjacent demyelinated paranode, and by day 11 the particle distribution is uniformly low over the entire extent of the nodal and demyelinated paranodal axolemma. If nodal E-face particles represent sodium channels, as has been proposed, the sequence of changes in Wallerian degeneration would be compatible with a gradual redistribution of nodal sodium channels into the demyelinated paranode.

Animals↗

PubMed1986

Ultrastructural localization of laminin in rat sensory ganglia.

We adapted immunocytochemical methods for localization of laminin to examine its disposition in neural tissue at the ultrastructural level. In dorsal root ganglia, laminin was found in basal laminae of the satellite and Schwann cells ensheathing neuronal perikarya and nerve fibers, respectively, and around blood vessels. Within the basal lamina, the immunostain was found in the lamina lucida and lamina densa. Occasional immunostained coated pits were identified in satellite and Schwann cells, but virtually no intracellular label was seen even in freeze-thawed/detergent-permeabilized specimens. In the perineurium, only the basal lamina of the inward-facing surface of the inner-most cell layer was usually stained.

Animals↗

PubMed1985

Dependence of axolemmal differentiation on contact with glial cells in chronically demyelinated lesions of cat spinal cord.

Chronically demyelinated lesions of cat dorsal columns were created by focal injection of the glial toxin ethidium bromide. Freeze-fracture studies show that the center of the lesion, which is devoid of glial cells and processes, contains axons having neither node-like nor paranodal-type membrane specializations. Near the margin of the lesion, however, where axons are in contact with glial cells, the axolemma sometimes displays focal accumulations of E- and P-face particles resembling those at nodes of Ranvier. In cases where the adjacent cell could be identified, it had the characteristics of an astrocyte. Linear indentations of the axolemma displaying a paracrystalline pattern like that of the paranodal axolemma also occur in the marginal region. Here, the adjacent cell had the characteristics of an oligodendrocyte. These specializations may be closely associated with each other or spatially separate. Normal nodal and paranodal specializations were absent throughout the lesion at all time periods examined. These findings support the view that both the formation and the maintenance of nodal and paranodal axon membrane specializations require contact with glial cells.

Animals↗

PubMed1985

Intramembranous particle patches in myelin-deficient rat axons.

Focal accumulations of E-face intramembranous particles occur in spinal cord axons of myelin-deficient rat mutants. These resemble nodal particles and, like them, may represent voltage-sensitive sodium channels. It is proposed that axonal activity at these foci could increase extracellular potassium to the point of triggering activity in adjacent axons. Rapid spread of such potassium-induced activity among bare axons could underlie the seizures and other neurological abnormalities that develop in this mutant. A similar mechanism may account for the paroxysmal attacks sometimes seen in multiple sclerosis.

Animals↗

PubMed1985

Plasma membrane structure at the axon hillock, initial segment and cell body of frog dorsal root ganglion cells.

Analysis of the plasmalemma of frog dorsal root ganglion cells by freeze-fracture demonstrates regional differences in the distribution of intramembranous particles. Although P-face particles are distributed rather uniformly, the E-face particle concentration at the cell body (approximately 300 micron -2) is much lower than that at the axon hillock (approximately 900 micron -2), proximal initial segment (approximately 1000 micron -2), or intermediate portion of the initial segment (approximately 800 micron -2). The particle concentrations in the latter regions approach that at the node of Ranvier and, moreover, particle size analysis reveals that the E-face particles, like those at the node, include a large number that are 10 nm or more in diameter. Thin sections reveal patches of a dense undercoating on the cytoplasmic surface of the axolemma in some regions of the initial segment but not the axon hillock. It is concluded from these results that the axon hillock and the initial segment of dorsal root ganglion cells have some of the structural characteristics of the node of Ranvier.

Animals↗

PubMed1984

Extranodal particle accumulations in the axolemma of myelinated frog optic axons.

Optic nerves of adult frogs were freeze-fractured with the proximal to distal orientation and distances from retina monitored throughout the process. E face particle accumulations are commonly found (approximately 90% of all examples) in the juxtaparanodal portion of the internode (JPI) immediately adjacent to the paranodal junction. The concentration of these particles is usually highest (200-700/micron 2) immediately adjacent to the last strip of the paranodal junction and then decreases over approximately 1-4 micron to the background level (approximately 100/micron 2) of the more remote portions of the internode. Accumulations with high particle concentrations generally extend further into the internode than those with low concentrations. JPI particle accumulations occur with equal frequency in proximal and distal JPIs, and no apparent difference was seen between optic nerve segments adjacent to or distant from the retina. The majority of the JPI particles are large (10 nm or more in diameter), and they resemble the large nodal particles in size and shape. Particle size analysis in different areas of the internode shows that the concentration of small particles does not change significantly along the internode (including the JPI), but the concentration of large particles is significantly higher in the immediate JPI (140-600/micron 2) than in internodal regions (30-55/micron 2). Thus, the high particle concentration at the JPI region is mainly due to the accumulation of large particles. Such accumulations also occur frequently in irregularly shaped 'lakes' between paranodal junctional strips. Here too the particles are primarily large, and the accumulations occur equally in segments adjacent to or distant from the retina and in both proximal and distal paranodal regions. Heminodes occur in all segments of the frog optic nerve. Most of these lack typical nodal specializations.

Animals↗