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K Kalil

Publications and source records attributed to K Kalil.

35 records · Page 2Linked to original sources
PubMed1988

Expression of two developmentally regulated brain-specific proteins is correlated with late outgrowth of the pyramidal tract.

The regulation of axon outgrowth is not well understood. In previous studies, however, axon elongation has been well correlated with expression of a small number of growth-associated proteins (GAPs). To identify other proteins whose expression could be correlated with axon outgrowth during development of CNS pathways, monoclonal antibodies were raised against growth cone particles isolated from neonatal hamster brains. Two of these antibodies recognized a brain-specific 33 kDa protein associated with intracellular membranes of axons and growth cones. Immunoblotting demonstrated a sharp developmental decline in levels of the protein in hamster brain during the first postnatal week and a more gradual decline thereafter. Immunocytochemical studies with the antibodies revealed ubiquitous staining of the neuropil during the first several days, which by the end of the first week became restricted to a few later-maturing pathways. Staining was most intense in the pyramidal tract and was well correlated with axon outgrowth, which continues until 14 d in this pathway. These results suggest that the 33 kDa protein may, like previously identified GAPs, play a role in axon elongation. Late outgrowth of the hamster pyramidal tract is also correlated with expression of another developmentally regulated protein, the high-molecular-weight neurofilament subunit (NF-H). Immunostaining with a monoclonal antibody that recognized phosphorylated NF-H demonstrated that this subunit does not begin to appear in the late-maturing pyramidal tract fibers until several weeks after birth, in striking contrast to intense immunoreactivity of other spinal cord pathways from postnatal day 1. This finding suggests that specific pathways may have a highly idiosyncratic time course for expression of neurofilament subunits.

Animals↗
PubMed1986

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↗
PubMed1985

Organization of motoneuronal pools in the rostral spinal cord of the sea robin, Prionotus carolinus.

The functional organization of the motoneurons in the spinal cord of the sea robin, Prionotus carolinus, was studied by means of retrograde transport of horseradish peroxidase (HRP). This species has a complex pectoral apparatus which includes not only a webbed fin, but also three independently mobile fin rays. The motoneurons in the rostral spinal cord fall into two longitudinal columns: dorsal and ventral. The motoneurons of the ventral column innervate the appendicular musculature of the pectoral apparatus. Within the ventral motor column of the rostral spinal cord, four distinct motoneuronal pools were found. The largest pool is situated at the rostral-most end of the spinal cord and contains the motoneurons that innervate the musculature of the webbed pectoral fin. The motoneurons that innervate the fin rays are located in sequentially more posterior pools so that the anteroventral fin ray is controlled by motoneurons situated farthest caudally. The somatotopic arrangement exactly corresponds to the sensory somatotopy determined previously. Furthermore, each fin ray has its sensory representation in a unique accessory spinal lobe which is connected in a reflex fashion to the motoneuronal pool that provides motor output to the same fin ray.

Animals↗
PubMed1985

Critical stages for growth in the development of cortical neurons.

In order to study the role of efferent connectivity in the development of CNS neurons, the growth of pyramidal tract neurons within the hamster sensorimotor cortex was studied during normal development and after early postnatal lesions of the pyramidal tract. We first determined, by a combination of Nissl and retrograde HRP techniques, that within the lumbar representation of cortical layer 5B in adult animals two cell populations exist: a large-celled population (40% of the total) projecting to the spinal cord and a small-celled population (60% of the total) projecting intracortically and to targets rostral to the medulla. We could not determine whether large layer 5B cells in the infant sensorimotor cortex also represent the corticospinal population. Nevertheless, measurements of the growth in cross-sectional area of the large cells from 7 days postnatal to adulthood showed that these cells continue to grow until 51 days of age. The most rapid rate of growth occurs between 7 and 14 days, during which time the cross-sectional area of the cell bodies triples, coincident with the arrival of corticospinal axons in the lumbar cord and the beginning of target innervation (Reh and Kalil, '81). The growth of the large neurons in layer 5B was then charted after the pyramidal tract was cut ipsilaterally in the medulla at various postnatal ages. Early lesions of the tract (4-8 days postnatal) interrupt lumbar projection fibers before they establish synapses in the cord. Nevertheless, cortical cell bodies in the lumbar representation continue to grow normally after axotomy until 11 days after birth. At this time, large cells are arrested in development and their cell size remains in the 11-day stage (50% of normal adult large cell size) indefinitely. In contrast, adult lesions of the tract cause a 60% shrinkage of large cells, which in the adult represent corticospinal neurons. No evidence for cortical cell death was found after pyramidal tract lesions at any age. The results of axotomy reveal a turning point in the development of layer 5B cortical neurons. Before the age of 11 days the large cells have an independent program of cell growth that proceeds despite axotomy. After this time, the large cortical neurons appear to require intact axons for further growth and, in the absence of normal connectivity, are arrested in development.

Age Factors↗
PubMed1982

A light and electron microscopic study of regrowing pyramidal tract fibers.

Autoradiographic and EM techniques were used to study the regenerative capacity of severed axons in the mammalian CNS. In infant and adult hamsters the pyramidal tract was severed unilaterally in the medulla several millimeters rostral to the decussation. After survival to adulthood, the animals received injections of [3H] proline in the sensorimotor cortex ipsilateral to the lesion. Autoradiography showed that labeled pyramidal tract axons in the medulla did not cross the lesion site. Instead, in animals with infant lesions there was massive new axonal growth arising from the severed pyramidal tract several millimeters rostral to the cut. Most of these labeled fibers crossed to the contralateral brainstem, coalesced into a compact bundle, descended just medial to the spinal trigeminal nucleus, and grew caudally for 6-7 mm. Although the trajectory of the regrowing axons was completely abnormal, their pattern of termination in the dorsal column nuclei and dorsal horn of the cervical spinal cord was normal. Synapse formation by the anomalous regrowing pyramidal tract axons in their appropriate terminal areas was confirmed by electron microscopy of terminal degeneration in animals with infant pyramidotomies followed by adult cortical lesions. Autoradiographic labeling of the new pathway at short postlesion survival times showed that the fibers grew out rapidly at about 1 mm/day, a rate somewhat slower than normal (2-4 mm/day). There was a dramatic difference in the capacity of the pyramidal axons to regrow in animals operated as infants vs. those operated as adults. The regrowth was maximal with lesions at 4-8 days of age. Capacity for new growth declined sharply thereafter such that after 20 days of age, pyramidal tract lesions elicited no new growth but instead a progressive axon degeneration retrograde to the lesion. These results, in contrast to many previous findings, show that significant regrowth of severed axons can occur in the neonatal CNS. Most importantly pyramidal tract fibers regrowing by anomalous routes can nevertheless establish synaptic connections in appropriate terminal areas and thus, as we show in the following paper, play a functional role in maintaining normal motor behavior.

Age Factors↗
PubMed1982

Functional role of regrowing pyramidal tract fibers.

When pyramidal tract axons are severed in the infant hamster, the damaged fibers regrow via a new pathway to their normal terminal sites in the medulla and spinal cord and there form synaptic connections (Kalil and Reh, '79, '82). We studied the behavior of animals with infant and adult lesions of the medullary pyramid to determine the functional significance of the new pathway in maintaining normal motor behavior. Examination of behaviors normally mediated by the pyramidal tract, particularly the manipulation of sunflower seeds during feeding, revealed a correlation between the presence of the new tract and the preservation of function. Furthermore, in the adult animal with an infant lesion, the spared behaviors were lost when the new pathway was destroyed.

Age Factors↗
PubMed1982

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↗
PubMed1981

Development of the pyramidal tract in the hamster. I. A light microscopic study.

The development of the pyramidal tract and other projections from the sensorimotor cortex was studied in the postnatal hamster with both (3H) proline and horseradish peroxidase (HRP) as anterograde tracers. In the 1-day-old animal labeled axons extend as far as the pons. Other corticofugal fibers have penetrated into the corpus striatum and the thalamus. By 2 days postnatally, the pyramidal tract has grown to midmedullary levels and there is substantial retrograde (HRP) and anterograde labeling in the thalamus. The pyramidal decussation is formed at 3 days of age and by 4 days the pyramidal tract has descended in the dorsal funiculus as far as midcervical spinal cord. Corticofugal fibers invade the pontine nuclei at 4 days and both the dorsal column nuclei and the superior colliculus at 6 days of age. At 6 days the pyramidal tract can be traced to mid-thoracic levels of the spinal cord, by 8 days the tract reaches lumbar levels, and by 14 days it has completed its caudal growth to the coccygeal spinal cord. Fibers first penetrate the gray matter of a given spinal cord level approximately 2 days after the tract has grown past that level in the dorsal funiculus. Pyramidal fibers continue their lateral growth into the dorsal horn at all levels of the cord throughout the third postnatal week such that by 21 days of age the pyramidal tract appears similar to that of the adult. The projections from sensorimotor cortex to the pontine nuclei, the superior colliculus, and the dorsal column nuclei appear to have a pattern similar to that of the adult soon after the fibers grown into these structures. There is a consistent delay of 2 to 3 days between the arrival of the pyramidal tract axons in the white matter adjacent to target structures and their innervation of a given terminal field. The pyramidal tract grows more quickly through the dorsal funiculus of the spinal cord than it does along the ventral surface of the medulla. Extensive elongation of pyramidal tract axons is achieved long before the growth and differentiation of the sensorimotor cortical neurons from which they originate. Finally, the pyramidal tract appears to grow as a compact bundle and not by the addition of temporally staggered groups of fibers. The relatively protracted period of innervation of the spinal cord by the pyramidal tract coupled with the immaturity of the cortical neurons at birth may be factors contributing to the significant regrowth of pyramidal tract axons severed early in development.

Aging↗
PubMed1981

Projections of the cerebellar and dorsal column nuclei upon the thalamus of the rhesus monkey.

Projections from the cerebellar and dorsal column nuclei to the midbrain and thalamus of the rhesus monkey were traced with anterograde autoradiographic techniques, or, in a few cases, with the Fink-Heimer method. The cerebellar nuclei give rise to a massive projection to the contralateral midbrain and thalamus via the ascending limb of the superior cerebellar peduncle. Cerebellar efferent fibers terminate contralaterally in both divisions of the red nucleus, and bilaterally in the interstitial nucleus of Cajal, the nucleus of Darkschewitsch, the oculomotor nucleus, and the central gray. All the deep cerebellar nuclei project upon a broad area of the contralateral ventral thalamus as well as certain intralaminar nuclei. Corresponding ipsilateral thalamic terminations are sparse. The topographic organization of cerebellothalamic fibers does not correspond to individual cerebellar nuclei or to cytoarchitectonic divisions of the ventral thalamic nuclei. Rather there are longitudinally oriented strips of terminal labeling which extend through all divisions of the ventral lateral nucleus, i.e., the VLps, the VLc, the VLo, as well as nucleus X, the oral division of the ventral posterolateral nucleus (VPLo), the central lateral nucleus (CL), and the most caudal region of the ventral anterior nucleus (VA). The topography of the cerebellothalamic fibers is arranged in a mediolateral pattern with fibers originating from anterior zones of the dentate and interpositus ending most laterally and those from posterior dentate and interpositus terminating most medially. The fastigial contribution is relatively sparse. The longitudinal strips of terminal labeling in the ventral thalamic nuclei are made up of still smaller terminal units consisting of disk-like aggregates of silver grains separated from one another by grain-free spaces. The dorsal column nuclei terminate primarily in the contralateral caudal division of the VPL (VPLc) and never extend rostrally into VPLo. These results demonstrate a segregation of cerebellar and dorsal columnar inputs to motor and sensory regions of the thalamus, respectively. Since these regions are separate and discrete in their cortical associations as well (Kalil, '76), it seems unlikely that fast afferent pathways relaying to motor cortex (Lemon and Porter, '76) could arise from the dorsal column nuclei.

Afferent Pathways↗
PubMed1979

Projections of the cerebellar and dorsal column nuclei upon the inferior olive in the rhesus monkey: an autoradiographic study.

Projections from the cerebellar and dorsal column nuclei to the inferior olive of the rhesus monkey were traced with anterograde autoradiographic methods. The cerebellar nuclei give rise to a massive projection which reaches the contralateral inferior olivary complex by way of the descending limb of the superior cerebellar peduncle. Dentato-olivary fibers project exclusively upon the principal olivary nucleus (PO) and observe a strict topography. The dorsal, lateral, and ventral dentate project respectively to the dorsal, lateral, and ventral lamellae of the PO. Within the lamellae, the dentato-olivary fibers are related point for point in the medio-lateral axis. By contrast, the rostro-caudal topography is reversed so that the rostral pole of the dentate projects to the caudal PO and the caudal dentate to the rostral PO. These connections are predominantly crossed but a small ipsilateral component recrosses the midline at the olivary commissure and mirrors the topography on the opposite side. The anterior interpositus projects only to the medial half of the DAO and the posterior interpositus projects only to the rostral two thirds of the MAO. The ipsilateral component is minor in comparison with the contralateral projection, but appears to be more substantial than the ipsilateral projection to the PO arising from the dentate nucleus. The fastigial nucleus does not project upon the olivary complex. The dorsal column nuclei project topographically upon the contralateral accessory nuclei with the gracile nucleus sending fibers primarily to the lateral half of the DAO and the cuneate nucleus projecting to rostral cell groups of the MAO. The present results when compared with other olivary connections described by previous studies in a variety of species suggest that regions of the MAO and DAO receiving sensory information from the periphery may lie outside the influence of cerebellar feedback loops.

Animals↗
PubMed1979

Regrowth of severed axons in the neonatal central nervous system: establishment of normal connections.

When pyramidal tract axons are cut in the adult hamster, fibers degenerate in both anterograde and retrograde directions from the lesion. If the same operation is performed on infant hamsters, however, there is massive regrowth of the severed axons via a new brainstem pathway to their appropriate terminal sites in the medulla and spinal cord. In contrast to previous studies, these results suggest that axons in the mammalian central nervous system damaged early in life may regenerate in a functionally useful way.

Age Factors↗
PubMed1975

A study of so-called 'retrograde fine-grain' degeneration in the thalamus.

Following lesions of the neocortex a uniform dust-like silver deposit may appear in certain thalamic nuclei stained with the Nauta or Fink-Heimer methods. Because this deposit lacks the characteristic morphology of axons undergoing Wallerian degeneration and often appears in regions of retrograde cell degeneration, it has been interpreted as a retrograde reaction7,15. The present study, however, employing reduced silver and autoradiographic techniques, suggests that this silver deposit is an anterograde rather than a retrograde phenomenon. In cats with lesions of the posterior cingulate and presubicular cortex the Fink-Heimer method showed the fine-grain silver deposit in the lateralis dorsalis (LD) and the anteroventral nucleus (AV). The 'dust' was densest in the dorsomedial zones of the anteroventral nucleus. After the survival times used (6-8 days) no retrograde perikaryal changes were seen in these nuclei. In other cats, 3 weeks after injections of radioactive proline in the posterior cingulate cortex, the distribution of the label in the LD and AV nuclei was almost identical to the distribution of the 'dust' in the Fink-Heimer sections. Since the autoradiographic method reveals anterograde transport, it appears that both methods are demonstrating corticofugal axons. Thus it is suggested that the 'fine-grain' degeneration arises from an anterograde not a retrograde reaction.

Animals↗
PubMed1975

Retrograde cortical aand axonal changes following lesions of the pyramidal tract.

Following lesions of the pyramidal tract in hamsters, retrograde changes were studied in the sensorimotor cortex and in the pyramidal tract axons proximal to the lesion, at survival times ranging from 2 weeks to 14 months. Severe cell shrinkage occurred in layer 5 pyramidal neurons as early as 2 weeks, but there was no cell loss among these neurons even with long survival times. Use of the Fink-Heimer method for degenerating axons revealed that the pyramidal tract proximal to the lesion had undergone a retrograde axon degeneration which, in some respects, resembled anterograde degeneration. The retrograde axon degeneration began at the lesion site and advanced slowly rostralwards with time involving increasingly greater numbers of fibers. However, even at the longest survival times the degeneration fell off markedly at pontine levels. The results indicate that this process represents a true retrograde fiber degeneration (as opposed to an indirect Wallerian degeneration) which appears to reach a point of equilibrium such that a partially shrunken pyramidal cell is maintaining a partially degenerated axon.

Animals↗