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Prelabeled red nucleus and sensorimotor cortex neurons of the rat survive 10 and 20 weeks after spinal cord transection.

To demonstrate definitively the fate of the somata of rubrospinal and corticospinal neurons axotomized by a complete spinal cord transection at T-9, in young adult rats we prelabeled the neurons by injection into the lumbar enlargement of a retrogradely transported fluorescent dye, Fluoro-Gold, and four days later transected the cord. We found no loss in cell number ten or 20 weeks after axotomy. The average size of the neurons in each case is slightly but significantly reduced. These findings unequivocally demonstrate that the somata of long tract neurons of the rubrospinal and corticospinal systems persist in an atrophic and presumably inactive state for at least 20 weeks, and raise the possibility that treatment of spinal cord injury may normalize cell activity and allow long tract regeneration.

Animals↗

Effects of red nucleus ablation and exogenous neurotrophin-3 on corticospinal axon terminal distribution in the adult rat.

Collateral sprouting of undamaged descending axons is one potential mechanism for recovery of function after incomplete spinal cord injury. In this study, we have investigated whether terminals of the intact corticospinal tract in the rat would sprout following ablation of a parallel descending pathway, the rubrospinal tract. No sprouting was detected after this injury alone. However, the combination of rubrospinal tract ablation with administration of 100ng neurotrophin-3 to neurons of the corticospinal tract resulted in marked increased density of corticospinal innervation in the superficial dorsal horn. There was no effect of administration of neurotrophin-3 alone and increase in axon density was not detected in the deep dorsal horn. These results imply that spontaneous sprouting of undamaged corticospinal axons does not occur following ablation of a parallel tract system, although collateral sprouting can be induced through a combination of the lesion plus exogenous growth factor. Induced change in corticospinal terminal density is detected in the superficial dorsal horn only, supporting the hypothesis that this is an area particularly supportive of circuit reorganisation.

Animals↗

Afterhyperpolarization in neurones of the red nucleus.

Afterhyperpolarization (AHP) following single or short trains of spikes in rubrospinal neurones (RN neurones) of the cat has been studied with intracellular recording techniques. The AHP amplitude was potential dependent; it increased with depolarization and decreased with hyperpolarization and had an extrapolated reversal potential about 20 mV below resting membrane potential. The AHP was associated with an increase in the membrane conductance and it was concluded that the AHP is primarily caused by an increase in membrane conductance to potassium ions. The time course of the conductance change underlying the AHP was measured with short current pulses and calculated from the AHP voltage. The AHP following a single spike was conditioned at different interspike intervals by a preceding spike (or several spikes). In many RN neurones the AHP (conductance) following a spike added approximately linear to that generated by a preceding spike. In most cells, however, the AHP following a spike was instead depressed by a preceding spike. The summation of AHPs increased progressively, while the depression appeared to be already maximal with one preceding spike. The depression was then approximately constant for interspike intervals less than the AHP duration. It will be shown in a following paper that these properties of the AHP are reflected in the behaviour of the repetitive discharge evoked by constant current pulses in the same neurones.

Action Potentials↗

Axon reaction in the red nucleus of the rat. Perikaryal volume changes and the time course of chromatolysis following cervical and thoracic lesions.

Two groups of 60 day old male Wistar Rats were subjected to right-sided rubro-spinal tractotomy at the fourth cervical and thirteenth thoracic vertebral levels respectively. Four animals in each group were sacrificed at each of the time intervals 1, 3, 4, 7, 14, 21 and 55 days. Counts of chromatolytic neurons from both groups of animals at time intervals ranging from 1-21 days established a time course for the chromatolytic response. Morphological observations showed a more severe central chromatolysis in the cervical group commencing at Day 3, and a much less severe central chromatolysis in the thoracic group starting at Day 4. By Day 21 the majority of the neurons of the cervical group were atrophic and by 55 days all were atrophic. The reaction following thoracic lesions was less intense and the maximum number of reacting neurons was observed at Day 7. Following this stage the neurons gradually returned to a normal morphological state which was complete by Day 55. Measurements of neuronal diameters from semi-thin Epon sections in the cervical group yielded statistically significant alterations in the perikaryal diameters of experimental neurons, demonstrating swelling at Days 1, 3 and 4 followed by shrinkage at Days 7, 14 and 21. The findings of this study suggest that the severity of the chromatolytic reaction in intrinsic neurons is intimately related to the distance of the lesion from the neuronal soma, while the time of onset of chromatolysis varies with lesion distance but is not directly proportional to it.

Animals↗

Development of distinct cell types in the feline red nucleus: a Golgi-Cox and electron microscopic study.

The feline RN contains neurons which fall into three size categories: giant (40--80 micrometer), medium (25--35 micrometer) and small (6--20 micrometer). These three populations of rubral neurons are distinguishable on the basis of a number of ultrastructural criteria and form classes not dissimilar from the traditional three divisions of cell types. Each of the three populations of rubral neurons can be further divided into three subgroups on the basis of a large number of configurational criteria discernible by the Golgi-Cox method. Each of these nine cell types are clearly separate, distinguishable by at least three criteria, and are found in different regions of the RN. It is shown that in the 5-day prenatal kitten, rubral neurons are already organized into the aforementioned three size categories. At this age most of the subpopulations are also distinguishable by the Golgi-Cox method. However, the giant rubral neurons (about 30 micrometer) and the medium sized cells (about 20 micrometer) are much smaller than in the adult cat. The dendrites elaborate many fine processes which emerge from multiple varicosities. The neuropil differs strikingly from that of the adult in that the vast majority of axons are small and unmyelinated. A number of changes in the RN are apparent as the kitten matures. The larger rubral cells undergo configurational changes before the smaller neurons, yet the giant cells continue to grow for a longer period of time. In the perinatal period, the extent of arborization of the dendritic trees diminishes, the number of spines decreases, and the long dendritic spines shorten. Somatic spines first appear in the giant cells at about one week after birth. In prenatal kittens, large cells frequently elaborate a tuft of fine branching processes in one region of the soma. These tufts later diminish in size and disappear by one week postnatal. Recent investigations (Pompeiano, '59; Condé, '66; King et al., '73' Sadun, '75) indicate that the RN of the cat is highly organized and very heterogenous. Afferent terminals are restricted to certain regions of certain cell types which are themselves specifically located within the RN. This specificity is apparent in perinatal kittens, despite the manifest immature appearance of the RN.

Animals↗

Anatomical organization of the limb premotor network in the turtle (Chrysemys picta) revealed by in vitro transport of biocytin and neurobiotin.

The in vitro turtle brainstem-cerebellum preparation has been a valuable tool in the study of central motor programs. In the present study, we investigate the anatomical organization of the turtle rubrocerebellar limb premotor network and its sensory connections in vitro by combining the rapid anterograde and retrograde transport of neurobiotin and biocytin with the extended viability of the isolated turtle brainstem-cerebellum. These compounds retrogradely labeled soma, dendrites, and axons, and orthogradely labeled axons and, to a lesser extent, terminals. The chelonian red nucleus receives a dense input from the contralateral lateral cerebellar nucleus and projects heavily to the contralateral spinal cord. Rubral axons sparsely innervate the lateral cerebellar nucleus and project heavily to the lateral reticular nucleus. Lateral reticular axons heavily innervate the lateral cerebellar nucleus before terminating in the pars lateralis of the cerebellar cortex as mossy fibers. These prominent, recurrent loops among the lateral cerebellar nucleus, red nucleus, and lateral reticular nucleus constitute the turtle rubrocerebellar limb premotor network. Sensory inputs to the red nucleus originate in the contralateral dorsal column nuclei, the principal trigeminal nucleus, and the spinothalamic system. These sites project bilaterally to the lateral reticular nucleus. The lateral cerebellar nucleus receives a contralateral input from the dorsal column nuclei. The red nucleus projects sparsely to the dorsal column nuclei. The red nucleus also receives an ipsilateral descending projection from the suprapeduncular nucleus, located in the diencephalon, and an ascending input from the rostral rhombencephalic reticular formation. An ipsilateral descending pathway originating in the red nucleus is likely to be the rubro-olivary tract.

Animals↗

Distribution of immunoreactive Met-enkephalin-Arg6-Gly7-Leu8 and Leu-enkephalin in discrete regions of the rat brain.

The distribution of immunoreactive (ir) leucine-enkephalin (LE) and ir-methionine-enkephalin-Arg-Gly-Leu (ME-RGL) in 101 microdissected rat brain and spinal cord regions was determined using specific and sensitive radioimmunoassays. The highest concentrations of LE and ME-RGL were measured in globus pallidus (5190 and 4378.8 fmol/mg protein, respectively). Very high concentrations of LE and ME-RGL (greater than 750 fmol/mg protein) were found in the central amygdaloid nucleus, anterior hypothalamic nucleus, lateral preoptic area, nucleus of the solitary tract (medial and commissural parts), bed nucleus of stria terminalis, dorsomedial nucleus, parabrachial nuclei, periaqueductal gray and motor hypoglossal nucleus. Very high concentrations of ME-RGL were found in 14 additional brain regions including medial preoptic area, area postrema, nucleus ambiguus, periventricular nucleus, ventromedial nucleus, interpeduncular nucleus, paraventricular, arcuate and others. High concentrations of LE (between 500 and 750 fmol/mg protein) were found in 15 brain areas, among them the periventricular nucleus, medial preoptic area, suprachiasmatic nucleus, dorsal premamillary nucleus, ventromedial nucleus, arcuate nucleus, nucleus ambiguus, locus coeruleus, substantia nigra. High concentrations of ME-RGL were measured in 13 brain areas including the suprachiasmatic nucleus, lateral septal nucleus, raphe magnus, motor facial nucleus, lateral amygdaloid nucleus, sensory trigeminal nucleus, nucleus accumbens, caudate-putamen. Moderate concentrations of LE (between 250 and 500 fmol/mg) were found in 46 brain areas such as the lateral septal nucleus, nucleus accumbens, caudate-putamen, several amygdaloid nuclei, supraoptic nucleus, the perifornical nucleus, posterior hypothalamic nucleus, red nucleus. Moderate concentrations of ME-RGL were detected in 27 areas such as the median eminence, nuclei of the reticular formation, supraoptic nucleus, red nucleus and others.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Brain nuclei and neurotransmitters involved in the regulation of the high pressure neurological syndrome in the rat.

The role of glutamatergic (NMDA), cholinergic and purinergic neurotransmission in the pedunculopontine nucleus, red nucleus, ventrolateral thalamic nucleus, entopeduncular nucleus, and the substantia nigra in the development of the high pressure neurological syndrome (HPNS) was investigated in the rat. Focal injection of D-2-amino-7-phosphonoheptanoate (D-APH, 5 nmol per side) into the red nucleus or the pedunculopontine nucleus was protective against HPNS-induced convulsions. Carbachol (10 nmol), injected into the red nucleus, did not influence the severity of the symptoms of HPNS. Injection of carbachol into the pedunculopontine nucleus, significantly lowered the threshold pressure for convulsions and increased the threshold pressure for tremor. 2-Chloroadenosine (5 nmol), injected into the red nucleus, produced a potent antitremorgenic effect and a similar but less pronounced effect when injected into the pedunculopontine nucleus. 2-Chloroadenosine, injected into the substantia nigra (12.5 nmol) or the ventrolateral thalamic nucleus (25 nmol), facilitated the development of tremor and, in the entopeduncular nucleus (25 nmol), facilitated the occurrence of convulsions. These results show the complexity of neurotransmitter interactions in different regions of the brain, under high pressure. They also indicate that the biochemical and anatomical substrates, involved in the convulsions produced by HPNS, differ substantially from those in other experimental models of epilepsy.

2-Amino-5-phosphonovalerate↗

Mechanisms of supraspinal correction of scratching generator.

The influences of signals in descending systems on the parameters of scratching generator activity were studied on decerebrate immobilized cats. It was shown that phasic electric stimulation of descending systems evoked certain phase-dependent reorganization of the parameters of scratching generator efferent activity. Maximum increase in scratching cycle duration during electric stimulation of Deiters' nucleus, red nucleus and pyramidal tract is observed during stimulation in the first half of aiming phase. Stimulation in the second half of aiming phase and at the beginning of scratching jerk phase virtually does not change the scratching cycle duration. Maximum increase in scratching cycle duration during electric stimulation of the nucleus reticularis gigantocellularis is observed in the second half of aiming phase. Electric activation of descending pathways during aiming phase increases its intensity and decreases the intensity of scratching jerk phase. Activation of descending pathways during scratching jerk phase increases its intensity and virtually does not change the aiming phase intensity. Influences of electric activation of descending systems on scratching generator work reveal dependence on limb position. They are increased when the limb is deflected to the rear and are decreased during over-aimed position. Decerebellation leads to a decrease of scratching generator activity parameters rearrangement under influence of electric stimulation of the red nucleus and nucleus reticularis gigantocellularis, and to its increase during Deiters' nucleus stimulation. On the basis of these results the principles of supraspinal correction of scratching generator work are discussed.

Animals↗

[Autopsy cases of hereditary ataxia pathologically diagnosed as the Japanese type of Joseph disease--cliniconeuropathological findings].

Two cases (father and son) clinically diagnosed as Menzel type of heredoataxia were examined pathologically, and found nonspecific, multisystem degenerations of central nervous system spreading from brain stem to cerebellum and spinal cord. Common neuropathological findings of both cases were marked neuronal loss, demyelination and cellular and fibrous gliosis in pallidum (esp. internal segment), body of Luys, substantia nigra, dentate nucleus, red nucleus, cranial and spinal motor nuclei, spinocerebellar tracts and Clarke's column. There were no abnormalities in cerebral cortex, caudate nucleus, putamen, thalamus and inferior olive nucleus. These findings had enough similarity to that of Japanese type of Joseph disease. The son who died 36 years old had showed clinically hyperreflexia, cerebellar ataxia, dystonic extrapyramidal movement, muscle atrophy and bulging eyes. Dominant pathological findings compared to the father case were neuronal loss of substantia nigra and red nucleus, fibrous gliosis of superior peduncles and grumose degeneration of dentate nucleus. The father case died 76 years old had showed hyporeflexia, cerebellar ataxia and no bulging eyes clinically. The pathologica findings of pallidum, cranial and spinal motor nuclei, dorsal column and spinocerebellar tracts were more dominant than the other reported case. Dementia, mental retardation, epileptic episodes were not found in this family pedigree. Pathological changes of pallidonigral, pallidoluysian, dentatorubral and spinal cord which were common in Japanese type were less found in original type of Joseph disease in Europe. Authors discussed this difference in relation with progressive pallidumatrophy, dentato-rubro-pallido-luisian atrophy and hereditary spastic ataxia. According to the classification of clinical feature of Joseph disease in Europe, the father case was classified as type III (Machado phenotype) and the son case was as type I (Joseph phenotype). Reported cases of type III and familial autopsy cases of Joseph disease were so rare in Japan, authors reported on their clinicopathological findings.

Adult↗

Descending systems contributing to locomotor recovery after mild or moderate spinal cord injury in rats: experimental evidence and a review of literature.

PURPOSE: Locomotor recovery after spinal cord contusion injury (SCI) may be mediated by descending axons spared at the lesion epicenter. Greater axonal sparing is associated with more extensive recovery. Therefore, we identified the source and relative proportion of spared axons associated with extensive or limited locomotor recovery after SCI. METHODS: Female Sprague Dawley rats underwent mild or moderate SCI using the OSU device. RESULTS: Locomotor recovery was greater for the mild than moderate group with the primary differences being restitution of limb coordination, very little toe dragging and minor paw rotation. CONCLUSIONS: The following brain nuclei with substantial neuronal labeling after mild but not moderate SCI may play an important role in locomotor recovery: raphe pallidus and magnus, ventral medullary and pontine reticular formation, lateral vestibular nucleus, red nucleus and locus coeruleus. We review the normal anatomical distribution of descending systems to the lumbar cord in rat and the role they play in motor control.

Animals↗

Inferior olivary hypertrophy is uncommon in progressive supranuclear palsy.

Inferior olivary hypertrophy (IOH) is an uncommon disorder attributed to transsynaptic degeneration and characterized clinically by palatal myoclonus and histopathologically by swollen, fenestrated neurons and bizarre astrocytic gliosis. IOH is usually associated with the interruption of the dentato-olivary tract, most often from cerebrovascular lesions in the dentate nucleus or red nucleus. In progressive supranuclear palsy (PSP), the dentato-olivary tract is consistently affected, and there are reports suggesting that IOH may be relatively common in PSP. To address this issue, the frequency of IOH was investigated in 264 PSP brains. To determine if there was a relationship between IOH and neurofibrillary degeneration in the dentato-olivary pathway, the severity of neurofibrillary degeneration was assessed in the inferior olivary nucleus, cerebellar dentate nucleus and red nucleus in PSP cases with and without IOH. IOH was uncommon in PSP, being found in only 4 of 264 (1.5%) brains, which was not significantly different from the frequency in non-PSP controls (8 of 862; 0.9%). In all non-PSP cases IOH was associated with cerebrovascular lesions, but not in any of the PSP cases with IOH. The severity of neurofibrillary degeneration in the inferior olivary nucleus was significantly greater in PSP cases with IOH than in PSP cases without IOH, whereas there were no significant differences in the cerebellar dentate nucleus and red nucleus. These findings suggest that direct neurofibrillary degeneration in the inferior olivary nucleus may be related to IOH in PSP rather than transsynaptic degeneration.

Adult↗

Involvement of the ventrolateral thalamic nucleus in rabbit classical eyeblink conditioning.

The involvement of the ventrolateral nucleus of the thalamus in relaying learning-related activity to higher brain structures during classical conditioning of the rabbit eyelid response was examined in two experiments. In the first study, multiple-unit ventrolateral thalamic nucleus activity was monitored before and after lesions of either the cerebellar interpositus nucleus or red nucleus were given. Before the lesions were given, conditioned response-related activity was observed in the ventrolateral thalamic nucleus. Lesions of the interpositus nucleus, but not the red nucleus, disrupted the conditioning-related activity in the ventrolateral thalamic nucleus, thus suggesting that an efferent copy of conditioned response-related activity is projected directly from the interpositus nucleus to higher brain areas by way of the ventrolateral thalamic nucleus. In the second study, multiple unit activity in the hippocampus was monitored before and after lesions were placed in the ventrolateral thalamic nucleus or red nucleus. Conditioning-related activity in the hippocampus was not affected by either lesion, thus suggesting that maintenance of training-related activity in the hippocampus is not critically dependent on cerebellar information relayed through the ventrolateral thalamic nucleus or red nucleus.

Animals↗

Immunohistochemical localization of intraneuronal transferrin receptor immunoreactivity in the adult mouse central nervous system.

Iron is essential for a variety of intracellular functions. Accordingly, the transfer of iron from blood to brain is vital for normal brain function. In the CNS, the receptor for iron-transferrin is generally accepted to be located in endothelial cells, whereas its occurrence in other cell types is less well established. I have investigated the distribution of the transferrin receptor in the adult mouse central nervous system by immunohistochemistry by using a monoclonal antibody raised against the transferrin receptor protein. Immunoreactive cell types comprised brain capillary endothelial cells, excluding those of circumventricular organs, and choroid plexus epithelial cells. Moreover, transferrin receptor immunoreactivity was detected intraneuronally in several brain regions without access to peripheral blood. The immunoreactive cell bodies were mainly confined to the cerebral cortex, hippocampus, habenular nucleus, red nucleus, substantia nigra, pontine nuclei, reticular formation, several cranial nerve nuclei, deep cerebellar nuclei, and cerebellar cortex. Transferrin receptor immunoreactivity was not detected in astrocytes, oligodendrocytes, or microglial cells. The occurrence of transferrin receptors at brain-barrier sites, i.e., the brain endothelium and choroid plexus epithelium, and the presence of the receptors intraneuronally are in accordance with the generally held belief that iron is released from liver transferrin and transported through capillaries and the choroid plexus into the brain interstitium. Subsequently, iron may be linked to brain transferrin synthesized within oligodendrocytes and choroid plexus epithelial cells followed by a concomitant uptake of iron-transferrin in neurons expressing transferrin receptors. The clinical importance of the intraneuronal transferrin receptor expression is discussed.

Animals↗

Regional and cellular distribution of the P2Y(1) purinergic receptor in the human brain: striking neuronal localisation.

The biological actions of extracellular nucleotides are exerted via two families of P2 receptors, P2X and P2Y. The metabotropic P2Y receptors comprise at least 7 distinct subtypes, which have been cloned from a number of species. However, none of the P2Y receptor proteins have been visualised yet in human brain. In the present study, the regional and cellular distribution of the P2Y(1) receptor was investigated in the human brain by using immunohistochemistry. Polyclonal antibodies were raised against a synthetic peptide from the C-terminus of the P2Y(1) protein. Immunoblot analysis demonstrated that P2Y(1) antiserum specifically recognised a 63-kDa band in human and rat brain membranes. Similarly, the antiserum specifically detected the human P2Y(1) receptor in transfected 1321N1 cells. Immunohistochemical analysis on perfusion-fixed human brain tissue showed a widespread distribution for this receptor throughout the brain. At the cellular level, the P2Y(1) receptor was strikingly localised to neuronal structures of the cerebral cortex, cerebellar cortex, hippocampus, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, red nucleus, and midbrain. Expression of the P2Y(1) receptor was not detected in other non-neuronal cell types. These results provide the first characterisation of the cellular distribution of a P2Y receptor in the human brain. The widespread and abundant distribution of the P2Y(1) receptor suggests its involvement in a number of important functions within the human brain. The neuronal localisation of this receptor points towards a possible role in neurotransmission, and also highlights a major role for extracellular nucleotides as signaling molecules within the brain.

Animals↗