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C E Hulsebosch

Publications and source records attributed to C E Hulsebosch.

67 records · Page 4Linked to original sources

Effects of nerve growth factor and its antibodies on sprouting of sensory axons following spinal cord hemisection.

Axons were counted in rat dorsal roots three segments cranial and three segments caudal to a spinal hemisection done at birth. The animals were placed in three groups: (1) hemisected (HEMI), (2) hemisected and given nerve growth factor (NGF) daily (HEMI + NGF) and (3) hemisected and given antibodies to NGF daily (HEMI + anti-NGF). They were sacrificed at 1 month. In the HEMI and HEMI + NGF groups, there were 20% and 13% more unmyelinated axons, respectively, in roots of the operated side. We interpret these differences to be the result of sprouting of unmyelinated axons as a result of denervation, and exogenous NGF does not seem to affect the response. By contrast, the unmyelinated axon responses in HEMI + anti-NGF animals are different. These animals have approximately 7% more unmyelinated axons on the denervated side and 50% more axons on the normal side than in the other animals we studied. The results on the anti-NGF animals are interpreted as indicating sprouting in response to a chemical denervation caused by NGF removal and the response is more dramatic on the unoperated side.

Animals↗

Increased numbers of thoracic dorsal root axons in rats given antibodies to nerve growth factor.

Sensory axons were counted in untreated 1-month-old rats and in littermates that were injected with antibodies to nerve growth factor. There were 45 percent more unmyelinated and 17 percent more myelinated axons in dorsal roots of the fifth thoracic spinal segment in treated rats. This suggests that the number of sensory axons can be changed by postnatal inactivation of nerve growth factor.

Aging↗

The effects of nerve growth factor and its antibodies on axonal numbers in the medial gastrocnemius nerve of the rat.

The effects of the administration of nerve growth factor (NGF) or its antibody (anti-NGF) on axonal populations in a peripheral nerve have been investigated. The nerve is a motor nerve, the nerve to the medial gastrocnemius muscle in the rat. The findings are that the administration of NGF at birth and for 28 days thereafter results in an increase of 42% of the unmyelinated axons in this nerve as compared to normal, and that the administration of anti-NGF in the same way results in a 20 and 30% decrease, respectively, in the myelinated and unmyelinated axons in this nerve. We speculate that the unmyelinated axon increase after NGF administration indicates an increase in post-ganglionic sympathetic axons and that the decreases in myelinated and unmyelinated axons after anti-NGF administration indicate decreases in both post-ganglionic sympathetic and sensory axons. The implications of these findings are discussed.

Animals↗

Effects of antibodies to nerve growth factor on sprouting following spinal cord hemisection in the rat.

Dorsal root unmyelinated axons in 30-day-old rats in which the spinal cord has been hemisected at birth are more numerous on the operated side in animals that receive preimmune serum daily from hemisection to sacrifice. This is interpreted as indicating that sprouting of sensory axons occurred on the operated side. In animals with hemisected cords treated daily with antibodies to nerve growth factor (anti-NGF), the same numbers of unmyelinated axons are found in the roots on the operated side, but there are even more unmyelanated axons on the unoperated side. Our interpretation is that anti-NGF results in sensory axon sprouting with more sprouts on the unoperated side. Thus removal of NGF in cord hemisected newborn rats has an effect on sensory axon numbers.

Animals↗

An empirical method for converting nucleolar counts to neuronal numbers.

Our goal is to estimate neuronal numbers from counts of nucleolar profiles. The primary difficulty is that a simple way to convert the counts to the numbers, especially when multiple nucleoli are present in a nucleus, is not available. In this paper, we propose a solution. The formula is N = n X [N(c.f.)/n(c.f.)] where N = the true number of neurons, n = the number of nucleolar profiles in these neurons, N(c.f.) = the number of neurons used to estimate the correction factor and n(c.f.) = the number of nucleolar profiles found in the neurons that make up N(c.f.). The constraints are that the neurons identified for N(c.f.) be representative of the entire population, N; that the nucleolar profiles be counted by the same criteria when n(c.f.) is determined as when n is determined, and that when the correction factor [N(c.f.)/n(c.f.)] is calculated, the nucleolar profiles in each neuron be counted only once. The advantages are simplicity, and generality; the latter resulting from the empirical nature of the correction factor which can calibrate for multiple nucleoli, split nucleoli, invisible fragments, nucleolar size changes, section thickness differences and any other factors that cause n to deviate from N.

Animals↗

Age related sprouting of dorsal root axons after sensory denervation.

To test for sprouting of dorsal root axons, 3 consecutive dorsal roots were sectioned above and 3 were sectioned below a spared root in rats 1 month and 24 months old. At various survival times, myelinated and unmyelinated axons were counted in the spared root, the first cranial root and the first caudal root, and these counts were compared to similar counts from the same roots on the unoperated side. The counts of myelinated axons in all roots and of unmyelinated axons in the caudal roots were not different from the counts in the same roots on the unoperated side. Thus there is no evidence for sprouting of these axons in our system. By contrast, the unmyelinated axons in the cranial and spared roots were significantly increased as compared to the unmyelinated axons in the same roots on the unoperated side. We interpret this increase to be sprouting of dorsal root axons. To determine the effects of age, animals operated at 1 month and sacrificed 1 month, 3 months or 18 months later were compared with animals operated at 2 years and sacrificed 1 month later. The unmyelinated axons were greater by approximately 20% on the operated side in the cranial and spared roots in the young rats and by approximately 8% in old rats. Thus the sprouting of unmyelinated axons is more vigorous when the surgery is performed in young animals, but there still seems to be a response in older animals.

Aging↗

A comparison of axonal numbers in dorsal roots following spinal cord hemisection in neonate and adult rats.

This study presents myelinated and unmyelinated axon counts from thoracic dorsal roots of rats whose spinal cords were hemisected at birth or at 1 year of age. Axonal numbers from a root on the unoperated side are compared to numbers from the root of the same segment on the operated side of the animal. Counts were made 3 segments cranially and 3 segments caudally from the hemisection. In animals hemisected at birth and sacrificed at 3-8 months, there is a statistically significant increase in unmyelinated axons in roots of the operated as compared to the normal side. We interpret this as sprouting of unmyelinated axons. In animals hemisected at 1 year of age, the statistically significant change was a drop in myelinated axons in roots of the operated side. We interpret this as a loss of myelinated axon cell bodies due to axon section in the dorsal funiculus. Thus axonal sprouting occurs in young rats in our paradigm and a loss of myelinated axons occurs in older animals. We emphasize that different axonal populations respond to hemisection in different ways at different times.

Age Factors↗

An analysis of the axon populations in the nerves to the pelvic viscera in the rat.

The present study uses selective surgical ablations combined with electron microscopic analyses to determine the number of axons in various categories in rat hypogastric, pelvic, and pudendal nerves, these being the nerves to the pelvic viscera in this animal. Unmyelinated fibers predominate in all of these nerves. One of the most significant findings is that the pelvic nerve contains almost as many postganglionic sympathetic fibers as the hypogastric nerve. Previous investigators thought that the pelvic nerve supplied the parasympathetic inflow and the hypogastric nerve the sympathetic inflow to the pelvic viscera. The finding that there is a sizable sympathetic component in the pelvic nerve negates this idea, at least for the rat, and presumably calls for a reevaluation of the syndromes that arise from pelvic as opposed to hypogastric nerve section. Other findings of interest are (1) that there are unmyelinated efferent axons in the pudendal nerve, indicating that the pudendal is not a typical somatic nerve, (2) that the hypogastric nerve has a very small sensory component, and (3) that there are fibers surviving in the distal stumps of all these nerves, particularly the pelvic and hypogastric nerves.

Adrenergic Fibers↗

Sprouting of dorsal root axons.

Sprouting of axons may be an important component in whatever restoration of neural tissue occurs following injury. A classic paradigm used to demonstrate sprouting is the spared dorsal root preparation. The present study determines the number of axons in the spared root, the cranial root and the caudal root as compared to their normal mates on the unoperated side of the spinal cord. The data confirm that sprouting occurs and the unmyelinated axons are the sprouting population in the dorsal root. The quantification of sprouting provides an opportunity to get a precise estimate of the parameters of sprouting and the hope is that this increased precision will lead to insights into functional changes that result from axonal sprouting.

Animals↗

Quantitation of sprouting of dorsal root axons.

The axonal sprouting that occurs after denervation resulting from a spinal hemisection can be quantified. Rats were subjected to hemisection of the spinal cord at birth, and the myelinated and unmyelinated axons in dorsal roots three segments cranial and three segments caudal to the lesion were counted 1 month after surgery. The number of unmyelinated axons in the dorsal root on the side of the hemisection increased 22 percent for the roots one segment from the lesion and 13 percent for the roots two and three segments from the lesion.

Animals↗

Morphology and number of neurons in two species of polychaetes.

Neurons of the ventral nerve cord (VNC) in the polychaete species Clymenella torquata and Nereis virens were ultrastructurally distinguished from glial cells by the smaller diameter and elongated shape of glial nuclei in adult organisms. In contrast to neurons, beta-glycogen-like particles and densely packed microfilaments were found in glial cytoplasm. Using these and other criteria, glial cells were distinguished from nerve cells in histologic preparations. All neuronal nuclei were counted in specified regions of the CNS of both polychaetes. In both species, the number of neuronal nuclei in various CNS regions remained constant in animals of very different body size. Since Clymenella has a set number of ganglia in the VNC and a set number of body segments, the total number of CNS neurons remains constant in adult members of this species. Since adult Nereis adds VNC ganglia in newly forming body segments, the total number of CNS neurons continuously increases, but the total number of CNS neurons in a ganglion does not change after it is formed.

Animals↗

Regeneration of axons and nerve cell bodies in the CNS of annelids.

The neuron addition hypothesis predicts that species that add CNS neurons during a particular ontogenetic stage should regenerate ablated somata better than species that add few, if any, neurons to the CNS during that same stage. We report that CNS nerve cells do not regenerate in three species of adult (reproductively competent) leeches (Hirudo medicinalis, Haemopus grande, and Macrobdella decora), which do not increase the number of neurons in any portion of the CNS. Nereis virens, a polychaete that adds CNS neurons to newly forming ganglia in the adult stage, also does not regenerate CNS neurons. Conversely, CNS neurons, including a pair of uniquely identifiable somata, do regenerate in Clymenella torquata, a polychaete that has a constant number of neurons in the adult stage. Hence, the results of our study suggest that several versions of the neuron addition hypothesis cannot predict CNS regenerative abilities in adult annelids. Finally, we report that severed stumps of CNS axons do not degenerate rapidly in Nereis or Clymenella, and that both species can regenerate severed CNS axons presumably by morphologic fusion or physiologic activation of surviving stumps.

Animals↗

Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: relation to central neuropathic pain.

Spinal cord injury (SCI) often leads to the generation of chronic intractable neuropathic pain. The mechanisms that lead to chronic central neuropathic pain (CNP) following SCI are not well understood, resulting in ineffective treatments for pain relief. Studies have demonstrated persistent hyperexcitability of dorsal horn neurons which may provide a substrate for CNP. We propose a number of similarities between CNP mechanisms and mechanisms that occur in long-term potentiation, in which hippocampal neurons are hyperexcitable. One biochemical similarity may be activation of the transcription factor, cyclic AMP response element-binding protein (CREB), via phosphorylation (pCREB). The current study was designed to examine whether tactile allodynia that develops in segments rostral to SCI (at-level pain) correlates with an increase in CREB phosphorylation in specific neurons known to be involved in allodynia, the spinothalamic tract (STT) cells. This study determined that, in animals experiencing at-level allodynia 35 days after SCI, pCREB was upregulated in the spinal cord segment rostral to the injury. In addition, pCREB was found to be upregulated specifically in STT cells in the rostral segment 35 days after SCI. These findings suggest one mechanism of maintained central neuropathic pain following SCI involves persistent upregulation of pCREB expression within STT cells.

Analysis of Variance↗