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Retrograde pyramidal tract degeneration in a patient with cervical haematomyelia.

Retrograde pyramidal tract degeneration has been described only very rarely in the human central nervous system. In most of these cases the thoracic or cervical corticospinal tracts were shown to have degenerated following long-standing, lower spinal cord lesions. In a 67 year old man, who lived 2 years following the rupture of a mid-cervical cavernous angioma, we observed such degeneration which reached as high as the pons. This axonal dissolution was much less manifest above the ponto-medullary junction. Large pyramidal cells of Betz were not identified in the precentral gyrus, suggesting that the parental soma of the damaged axons had undergone atrophic changes. Furthermore, the involvement of the so-called aberrant pyramidal tract in the pontine medial lemniscus indicated that retrograde degeneration had occurred there as well.

Aged↗

B-50/GAP43 is localized at the cytoplasmic side of the plasma membrane in developing and adult rat pyramidal tract.

The neuron-specific phosphoprotein B-50/GAP43 has been implicated in axonal outgrowth, since high levels of B-50/GAP43 are found in growth cones and during development of the nervous system. In adult brain, the B-50 levels are decreased. B-50 is primarily found in axons and presynaptic terminals. It is phosphorylated by protein kinase C, and this process has been implicated in the modulation of membrane signal transduction. During the outgrowth of the pyramidal tract, high levels of B-50 have been reported, whereas a low amount of B-50 persists into the adult stage. By immunoelectron microscopy, using immunogold labeling on cryosections and pre-embedding peroxidase labeling, we examined the distribution of B-50 in the pyramidal tract at the third cervical segment in developing 2-d-old and adult 90-d-old rats. B-50 immunoreactivity was found in axons and growth cones of the outgrowing tract. In the adult pyramidal tract, both unmyelinated and myelinated axons contained B-50 immunoreactivity. The immunogold label was predominantly located at the plasma membrane. Since the peroxidase reaction product was observed exclusively intracellularly, we conclude that the B-50 immunoreactivity is predominantly located at the cytoplasmic side of the plasma membrane of axons and growth cones. The high immunoreactivity in growth cones and axons of the outgrowing pyramidal tract further supports the hypothesis that B-50 plays a role in neurite outgrowth. The presence of B-50 in the adult pyramidal tract cannot merely be attributed to transport to the synapse. Therefore, it is suggested that B-50 plays, in addition, a local, growth-associated role in the adult tract.

Aging↗

Distribution of effective synaptic currents in cat triceps surae motoneurons. VI. Contralateral pyramidal tract.

We measured the effective synaptic currents (IN) produced by stimulating the contralateral pyramidal tract (PT) in triceps surae motoneurons of the cat. This is an oligosynaptic pathway in the cat that generates both excitation and inhibition in hindlimb motoneurons. We also determined the effect of the PT synaptic input on the discharge rate of some of the motoneurons by inducing repetitive firing with long, injected current pulses during which the PT stimulation was repeated. At resting potential, all but one triceps motoneuron received a net depolarizing effective synaptic current from the PT stimulation. The effective synaptic currents (IN) were much larger in putative type F motoneurons than in putative type S motoneurons [+4.6 +/- 2.9 (SD) nA for type F vs. 0.9 +/- 2.4 nA for putative type S]. When the values of IN at the threshold for repetitive firing were estimated, the distribution was markedly altered. More than 60% of the putative type S motoneurons received a net hyperpolarizing effective synaptic current from the pyramidal tract stimulation as did 33% of the putative type F motoneurons. This distribution pattern is very similar to that observed previously for the effective synaptic currents produced by stimulating the contralateral red nucleus. As would be expected from the wide range of IN values at threshold (-4.8 to +8.7 nA), the PT stimulation produced dramatically different effects on the discharge of different triceps motoneurons. The discharge rates of those motoneurons that received depolarizing effective synaptic currents at threshold were accelerated by PT stimulation (+1 to +8 imp/s), whereas the discharge rates of cells that received hyperpolarizing currents were retarded by the PT input (-2 to -7 imp/s). The change in firing rates produced by the PT stimulation was generally approximated by the product of the effective synaptic currents and the slopes of the motoneurons' frequency-current relations. Our findings indicate that the contralateral pyramidal tract may provide a powerful source of synaptic drive to some high-threshold motoneurons while concurrently inhibiting low-threshold cells. Thus this input system, like that from the contralateral red nucleus, can potentially alter the gain of the input-output function of the motoneuron pool as well as disrupt the normal hierarchy of recruitment thresholds.

Animals↗

Visualization of the pyramidal tract in glioma surgery by integrating diffusion tensor imaging in functional neuronavigation.

OBJECT: The aim of this study was to investigate whether diffusion tensor imaging (DTI) can be integrated into functional navigation for the intraoperative visualization of the pyramidal tract. METHODS: A single-shot spin-echo diffusion-weighted echo planar imaging sequence on a 1.5 T magnetic resonance (MR) scanner was used for DTI. One null image and six diffusion-weighted images (high B value 1 000 mm/s (2)) were obtained. Color-encoded fractional anisotropy maps of the principal eigenvector rendered as a boxoid within each voxel were used for segmentation of the pyramidal tract. The segmented images were rigidly registered with a T(1)-weighted gradient echo 3D dataset for navigation in 16 patients with gliomas. In tumors adjacent to the motor cortex (n = 6) data from functional MR imaging were co-registered. RESULTS: The whole DTI processing lasted about 25-30 minutes in each case. In all cases DTI could be integrated into the navigational dataset resulting in an intraoperative visualization of the pyramidal tract by microscope-based navigation. Navigational accuracy measured as the target registration error was 1.2 +/- 0.46 mm. Registration of fractional anisotropy maps with the 3D navigational dataset was possible with an error of less than 2 mm. Co-registration with fMRI was consistent with DTI data. A neurological deterioration was observed only in one patient. CONCLUSIONS: DTI can be reliably integrated into navigational datasets. Thus, microscope-based neuronavigation can be used for an intraoperative visualization of the course of the pyramidal tract. However, a possible shifting of the pyramidal tract has to be taken into account after major tumor parts are removed.

Adolescent↗

Morphological and electrophysiological characteristics of pyramidal tract neurons in the rat.

Responses evoked in neurons of rat sensorimotor cortex upon stimulation of the pyramidal tract and ipsilateral cerebral peduncle were analysed using intracellular recording. Neurons responding antidromically to pyramidal tract stimulation (PT cells) and neurons failing to respond antidromically but exhibiting orthodromic responses were both stained by intracellular injection of horseradish peroxidase (HRP). Layer V pyramidal neurons, including those responding antidromically, exhibited prominent long lasting membrane hyperpolarizations and inhibitions of action potentials following pyramidal tract or cerebral peduncle stimulation. Upon passage of polarizing intracellular current two components were identified within the hyperpolarizing potential. A short duration initial component readily reversed with hyperpolarizing current. Frequently this earlier component overlapped a period of early excitation consisting of action potentials arising from recurrent EPSPs or large slow depolarizing potentials (SDPs). The second, much longer duration hyperpolarizing component did not reverse with passage of hyperpolarizing current and was often followed by a rebound period of depolarization and action potential generation. Both the excitatory and the inhibitory portions of these responses could be demonstrated in animals with acute thalamic transections severing the ascending lemniscal pathway to cortex. Following intracellular staining with HRP, two types of PT cells were identified by their different intracortical axonal arborizations. Most of the injected neurons had local axonal fields extending widely in layers V and VI, but with few or no collaterals extending radially toward the more superficial layers. A second type of PT cell had axon collaterals limited to a narrow zone around the dendritic field but extending radially as far as layer I. Cells of both types were observed to send axon collaterals into neostriatum. Both types of neurons exhibited morphological and physiological characteristics of slow PT cells, and we could find no cells comparable to the fast conducting PT cells observed in other species.

Animals↗

The effects of unilateral pyramidal tract section on hindlimb motor performance in the rat.

Most investigations on selective lesions of the pyramidal tract in rodents have focused on the functional impairment of the forelimbs. This study describes the effects of a unilateral transection of the pyramidal tract rostral to the decussation on hindlimb function. Using kinematic locomotion analysis, the narrow beam test, open field locomotion ranking, analysis of footprints and air righting, we found severe impairments including hypermetria, trunk instability, lateral shifts in weight support, toe dragging, and hindlimb exo-rotation. Most impairments recovered rapidly within the first week after operation. Slight hypermetria persisted after 4 weeks. The rather mild long term deficits after unilateral pyramidotomy may stress the need for extremely sensitive behavioural tasks to enable the detection. We conclude that the possibility to correlate regenerative changes following selective pyramidal tract lesions with hindlimb function is thus limited.

Animals↗

Modulation of cortical and pyramidal tract induced motor responses by electrical stimulation of the basal ganglia.

Two general mechanisms based on anatomical studies are possible for modulation of motor activity by the caudate nucleus and globus pallidus. These mechanisms are: (1) modulation of the output of cortical neurons that exert motor influences; and (2) modulation of subcortical neurons that exert motor influences. Differentiation between these two mechanisms was accomplished in the present study by two experimental approaches, both of which employed the conditioning-test paradigm. The first approach was an investigation of caudate nucleus or globus pallidus modulation (conditioning stimulus) of flexor responses of the anterior tibialis muscle elicited by electrical stimulation of the sensorimotor cortex (test stimulus) or pyramidal tract (test stimulus). These investigations were carried out in the intact and in decorticate cats. The second approach was an analysis of modulation or cortically induced pyramidal tract responses (direct and indirect, D-I potentials) by conditioning shock trains delivered to various loci within the caudate nucleus or globus pallidus. Both approaches were designed to determine whixh inhibitory and facilitatory motor influences of the basal ganglia occurred at a cortical or subcortical level. Simultaneous stimulation of a locus within the caudate nucleus and the sensorimotor cortex evoked either an enhancement, reduction or no alteration of the cortically induced increase in flexor responses (measured by Ia afferent activity, EMG, myogram). In contrast, no inhibitory influences occurred from caudate nucleus stimulation upon pyramidal tract induced flexor responses in either the intact or decorticate preparation. Inhibitory loci were distributed toward the rostral portion of the caudate nucleus, whereas facilitatory loci were distributed throughout; this distribution was statistically significant (chi2; P less than 0.01). Only enhancement or no influence upon cortical induced or pyramidal tract induced responses were obtained by conditioning stimuli to the globus pallidus. In the unanesthetized but immobilized cat, trains of shocks delivered to the caudate nucleus enhanced, reduced or had no influence upon the cortically evoked direct (D) and indirect (I) potentials recorded in the bulbar pyramidal tract. The distribution of facilitatory and inhibitory loci was organized in a similar fashion as in theanesthetized preparation. From these observations, a model was proposed in which the output of the caudate nucleus exerts both facilitatory or inhibitory modulation of the tonically active globus pallidus cells. The latter in turn predominantly or exclusively facilitate output of pyramidal tract neurons as well as the output of subcortical structures; both effects facilitate motor responses at the spinal level.

Animals↗

The physiological identification of pyramidal tract neurons within transplants in the rostral cortex taken from the occipital cortex during development.

Axons from neurons in the occipital cortex transiently extend to the pyramidal tract (PT) during the early postnatal development of rats. Normally, these axons are eliminated by the end of the third postnatal week. However, if a portion of fetal occipital cortex is transplanted to the parietofrontal region in newborn hosts then some neurons in the transplant will extend pyramidal tract axons and maintain them. Intracortical microstimulation and electrophysiological recording techniques were used to identify the physiological characteristics of the transplanted pyramidal tract cells and to determine if motor effects could be elicited from the occipital transplant. Microstimulation of the transplant did not reliably evoke movement but the low density and disarray of PT cells within the transplant might account for this. Recording from within the transplant revealed that the overall cell activity was depressed. We were able to identify neurons within the transplant which responded antidromically to stimulation of the pyramidal tract, indicating that their axons have the capacity to conduct impulses and are therefore likely to have developed some viable connections. The functional significance of such projections remains uncertain.

Animals↗

In vivo 3D visualization of normal pyramidal tracts in human subjects using diffusion weighted magnetic resonance imaging and a neuronavigation system.

We describe the potential of anisotropic diffusion weighted imaging to visualize the course of large cerebral fiber tracts. Five healthy volunteers were investigated at a field strength of 1.5 Tesla, employing a spin-echo diffusion weighted sequence with gradient sensitivity in six non-collinear directions to visualize the course of the pyramidal tracts. The pyramidal tracts were segmented and reconstructed for three-dimensional visualization. Reconstruction results together with a fusioned high resolution 3D T1 weighted image data set were available in a customized neuronavigation system. Origination in the primary motor cortex, convergence in the centrum semiovale, the posterior limb of the internal capsule, the cerebral peduncles, the splitting at the level of the pons, and the pyramidal decussation were identified in all subjects. Fiber tract maps might have the prospect of guiding neurosurgical interventions, especially when being linked to a neuronavigation system. Other potential applications include the demonstration of the anatomical substrate of functional connectivity in the human brain.

Adult↗

Pattern of myelination in the pyramidal tract of the rat.

The size and myelination of midbulbar pyramidal tract axons were measured by electron microscopy in the rat. We found that myelin thickness did not increase linearly with fiber size; rather, it took on certain preferred thicknesses almost independently of fiber size. This pattern of growth and development is fundamentally different from that of peripheral nerve and may be important for the physiology of the pyramidal tract.

Animals↗

Pyramidal tract damage correlates with motor dysfunction in bilateral periventricular leukomalacia (PVL).

In children with periventricular leukomalacia (PVL), motor dysfunction is thought to be related to involvement of pyramidal tract fibres in the periventricular white matter. The purpose of the present study was to test this hypothesis. Thirteen former preterm adolescents with PVL, ten of whom were suffering from bilateral spastic cerebral palsy, were studied by MRI. The severity of pyramidal tract damage was assessed on semicoronal MRI reconstructions along anatomical landmarks of somatotopy in the precentral gyrus and the internal capsule; for comparison, the overall volume of cerebral white matter (determined by automated volumetry) served as a global measure of lesion severity. The motor dysfunction of each of the four extremities correlated much more strongly with the severity of pyramidal tract damage assessed on the respective MRI reconstruction (range of correlation coefficients, 0.647 to 0.922) than with the total volume of white matter (range of correlation coefficients, - 0.458 to - 0.212; Spearman). These findings corroborate the notion that an involvement of pyramidal tract fibres in the periventricular white matter is indeed a relevant factor for motor dysfunction in children with PVL.

Adolescent↗

Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke.

We used diffusion tensor imaging (DTI) to assess Wallerian degeneration of the pyramidal tract within the first 2 weeks after ischemic stroke, and correlated the extent of Wallerian degeneration with the motor deficit. Nine patients with middle cerebral artery stroke were examined 2-16 days after stroke by DTI and T2-weighted MRI. We measured fractional anisotropy (FA), averaged diffusivity (Dav), eigenvalues of the diffusion tensor and T2-weighted signal in the cerebral peduncle and compared these values between the affected and the unaffected side and between patients and six controls. FA was significantly reduced on the affected side compared to the unaffected side and compared to the control group. The largest eigenvalue was reduced, whereas the smallest eigenvalue was elevated on the affected side. There was no significant difference in T2-weighted signal and Dav. The decrease of anisotropy correlated positively with the motor deficit at the time of DTI study and 90 days after stroke. The reduction of anisotropy mirrors the disintegration of axonal structures, as it occurs in the early phase of Wallerian degeneration. DTI detects changes of water diffusion related to beginning pyramidal tract degeneration within the first 2 weeks after stroke that are not yet visible in conventional T2-weighted or orientationally averaged diffusion weighted MRI. We demonstrated for the first time a correlation of early DTI findings of pyramidal tract damage with the motor deficit. DTI can help prognosing recovery of motor function after stroke within the early subacute phase.

Aged↗

Elevated synthesis of an axonally transported protein correlates with axon outgrowth in normal and injured pyramidal tracts.

Axons of the adult mammalian CNS typically fail to regenerate after injury. Among the hypotheses to account for this failure is the proposition that certain axonal proteins necessary for axon growth are expressed in much greater abundance in developing than in mature neurons, and that these proteins are not reinduced after injury to mature axons (Skene and Willard, 1981b). In the present experiments, we have found that hamster pyramidal tract neurons synthesize an acidic, 43K protein that is transported into growing axons during the first 2 weeks of postnatal development, and then declines at least an order of magnitude by the fourth postnatal week. The decline in synthesis of the 43K protein coincides with the cessation of pyramidal tract axon elongation. This protein resembles a "growth-associated protein," GAP-43, which is induced during regeneration of CNS axons in lower vertebrates. The 43K protein in hamster pyramidal tract neurons is not reinduced after axotomy in adult animals, which correlates with the failure of the injured axons to regenerate. Injury to neonatal pyramidal tract axons does not reverse or delay the decline in 43K protein synthesis. This is consistent with previous findings (Kalil and Reh, 1982) that pyramidal tract axons regrow for only a brief period after neonatal injury. Taken together, these results lend support to the hypothesis that synthesis of GAP-43 is important for axon growth in development and regeneration.

Animals↗

[Changes in the direct and interhemispheric responses of the pyramidal tract after tetanization of the cortex and lateral hypothalamus].

Changes in pyramidal tract response after unilateral neocortical and lateral hypothalamic tetanization were analyzed in unanesthetized and nonimmobilized rabbits. Membrane and synaptic modifications were revealed in intra- and interhemispheric connections. Changes in excitability of callosal collaterals of pyramidal tract neurons in contralateral hemisphere and changes in somatodendritic excitability in ipsilateral hemisphere could be oppositely directed. Plasticity of callosal connections may contribute to the interhemispheric asymmetry during learning.

Animals↗

Aberrant pyramidal tract in the medial lemniscus of the human brainstem: normal distribution and pathological changes.

We examined the consistency of the so-called aberrant pyramidal tract (APT) in 150 consecutive autopsied human brains using the modified Bielschowsky stain for axons. We were able to identify the APT in all brains except for one with holoprosencephaly. The APT left the pyramidal tract within the crus cerebri and passed in the medial lemniscus of the pons through the upper medulla oblongata. In 13 of the 63 brains with cerebrovascular diseases, wallerian degeneration was found in the APT on the ipsilateral side of the cerebral lesions. Further, the APT showed depletion of small-sized fibers in 2 of the 5 brains with multiple-system atrophy. These findings confirmed that the APT is a normal descending fiber tract and a part of the pyramidal tract.

Adult↗

Development of the pyramidal tract in the hamster. II. An electron microscopic study.

We undertook a qualitative and quantitative electron microscopic study of the growth and development of the pyramidal tract in the hamster to investigate the mode of growth of the axons, the possibility of fiber degeneration during development, and the process of myelination. By calculating the total fiber number as the product of axon density and tract area for several postnatal ages, we found that the pyramidal tract grows through the medulla as a compact bundle containing nearly twice the number of fibers as the mature tract. During the second postnatal week there is a substantial loss of axons followed in the third and fourth weeks by a more gradual loss such that by 34 days after birth the total number of axons reaches the adult value. Myelination in the hamster pyramidal tract begins at 7 days and continues at a very slow rate until the third postnatal week, when a dramatic increase in myelin formation occurs. By 34 days after birth the number of myelinated axons is approximately 80% that of the adult. as has been reported for other CNS tracts, there does not seem to be a "critical diameter" of an axon that absolutely determines the presence or absence of myelin on a fiber. However, all axons above 0.5 micron in diameter are myelinated at approximately the same rate, while those under this diameter are myelinated much more slowly and even in the adult make up only a small percentage of the total myelinated fibers.

Animals↗

A detailed morphometrical analysis of the pyramidal tract of the rat.

The present study is aimed at a quantitative analysis and comparison of the fibers of the pyramidal tract of the rat at two levels: the pyramis medullae and the second cervical segment. For this purpose both levels of the pyramidal tracts of 5 rats have been studied morphometrically at the ultrastructural level. Fiber numbers as well as fiber diameter distributions are presented for both myelinated and unmyelinated axons. At the level of the pyramis medullae the number of unmyelinated fibers (140,000 +/- 7000) exceeds the number of myelinated axons (103,000 +/- 6000). In contrast at the level of the second cervical segment the numbers of fibers of the axon populations studied are not significantly different, viz. 43,000 +/- 2000 myelinated and 35,000 +/- 8000 unmyelinated fibers. However, these numbers mean a significant decrease of myelinated axons (48%) compared with the pyramis medullae level and an even much larger decrease (75%) in the numbers of unmyelinated fibers. Diameter distributions, obtained from the minimal fiber diameter, show a similar, monomodal shape for all axon and myelin profiles. For unmyelinated axons the minimal diameter ranges from 0.05 to 1.21 micron with a mean of 0.18 +/- 0.03 micron. For myelinated axons a mean minimal diameter of 0.72 +/- 0.12 micron has been found (range 0.13-4.92 micron), whereas their diameter measured with myelin sheath measure 1.08 +/- 0.13 micron (range 0.25-6.03 micron). The average thickness of the myelin sheath is 0.2 micron and is strongly correlated to axon diameter. Furthermore, g-ratio has been computed at a mean of 0.65 and is fairly constant throughout the diameter spectrum. Several possibilities concerning the functional and anatomical qualities of the numerically important unmyelinated axon population in the pyramidal tract of the rat are discussed.

Animals↗