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At least 973 records · Page 54Linked to original sources
PubMed2000

Chondroitinase ABC promotes axonal regeneration of Clarke's neurons after spinal cord injury.

We examined whether enzymatic digestion of chondroitin sulfate (CS) promoted the axonal regeneration of neurons in Clarke's nucleus (CN) into a peripheral nerve (PN) graft following injury of the spinal cord. After hemisection at T11, a segment of PN graft was implanted at the lesion site. Either vehicle, brain-derived neurotrophic factor (BDNF) or chondroitinase ABC was applied at the implantation site. The postoperative survival period was 4 weeks. Treatment with vehicle or BDNF did not promote the axonal regeneration of CN neurons into the PN graft. Application of 2.5 unit/ml chondroitinase ABC resulted in a significant increase (12.8%) in the number of regenerated CN neurons. Double labeling with Fluoro-Gold and NADPH-diaphorase histochemistry showed that the regenerated CN neurons did not express nitric oxide synthase (NOS). Our results suggest that CS is inhibitory to the regeneration of CN neurons following injury of the spinal cord.

Animals↗
PubMed2000

Functional human heme oxygenase has a neuroprotective effect on adult rat ganglion cells after pressure-induced ischemia.

Adult retina subjected to transient ischemia and reperfusion leads to controlled retinal ganglion cell (RGC) death over a period. Modification of intracellular mechanisms through a specific adenoviral vector containing the hemoxygenase gene (HO-1) provides avenues for RGC survival following HO-1 gene transfer and ischemia. RGC death rate was reduced by an average of 15% at 1, 2 and 3 weeks. A significant number of RGC transfected with functional HO-1 survived ischemic insults. Pharmacological stimulation of HO-1 may constitute a novel therapeutic approach to rescuing RGC experiencing ischemic/reperfusion injury.

Adenoviridae↗
PubMed2000

CNTF promotes the regrowth of retinal ganglion cell axons into murine peripheral nerve grafts.

Autologous peripheral nerves were transplanted onto transected optic nerves of adult mice. We examined whether intraocular CNTF injections increased retinal ganglion cell (RGC) axon regeneration, and what types of RGCs regrew axons into grafts. After temporal CNTF eye injections there were more fluorogold-labelled regenerating RGCs (mean +/- s.e.m. 342+/-113.1; n=6) than in sham eye-injected mice (133+/-27.6; n=8). Greater numbers of regenerating RGCs (1198+/-367.6; n=6) were seen in mice receiving both nasal and temporal CNTF injections. The range of soma areas in regenerate and normal retinas was similar but the average size of regenerating RGCs was greater (212 microm2 vs 111 microm2). Most regenerating RGCs had large dendritic fields. The data suggest a heterogeneous response to axotomy in adult mice, large RGCs preferentially regrowing axons into PN grafts.

Animals↗
PubMed2001

Sex-induced fos in the medial preoptic area: projections to the midbrain.

Sexual activity results in cells displaying Fos-like Immunoreactivity (FLI) in the medial preoptic area (MPOA) of male rats. This study combined retrograde tracing techniques with FLI to determine if MPOA cells displaying sex-induced FLI project to known efferent sites of the MPOA. FluoroGold was injected into the dorsal central gray, lateral central gray, ventral tegmental area, medial central tegmental field, or lateral central tegmental field of male rats that later engaged in sexual activity. Examination of FLI and FluoroGold in the MPOA revealed that the lateral region of the MPOA projected to the lateral central gray and contained smaller projections to the other regions. These findings suggest that the lateral MPOA contains secondary sex-relevant projections to the midbrain.

Animals↗
PubMed2002

Development of the regenerative capacity of postnatal axotomized rat spinal motoneurons.

The present study examined whether a peripheral nerve (PN) graft can rescue developing motoneurons from degeneration and determined when immature motoneurons begin to express a regenerative capacity. Transplantation of a PN graft was unable to rescue motoneurons from degeneration if spinal root avulsion was performed in animals younger than P14. However, this procedure did enhance motoneuron survival when root avulsion was performed at P14 or later. Immature (P1 or P7) motoneurons were unable to regenerate their axons into the transplanted PN graft following root avulsion, whereas in older animals (P14-P28) motoneurons were able to regenerate axons into the PN graft. The percentage of regenerated motoneurons increased from P21 to P28 and was similar to that of adult animals. Therefore, the regenerative capacity of rat spinal motoneurons first begins at about P14, which seems to be critical.

Aging↗
PubMed1989

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↗
PubMedDate not supplied

Systemic blastomycosis in children.

Ten pediatric patients with systemic blastomycosis in Arkansas are reviewed. No particular age predisposition in childhood is apparent and there has been no change in incidence over the previous 40 years. Six of the 10 cases were male and 8 were black. Organ systems most commonly involved were pulmonary, skeletal and skin. With current therapy, usually amphotericin B as a single agent, the case fatality rate is less than 10%. Early recognition and institution of appropriate antifungal treatment remain the most important factors for survival and prevention of chronic pulmonary disease.

Adolescent↗
PubMed1999

Sensory innervation of the dorsal portion of the lumbar intervertebral disc in rats.

STUDY DESIGN: The vertebral levels of dorsal root ganglia innervating the dorsal portion of the L5-L6 intervertebral disc were investigated in rats using a retrograde transport method. The pathways and functions of nerve fibers supplying the dorsal portion of the disc were determined by denervation and immunohistochemistry. OBJECTIVES: The dorsal portion of the lumbar intervertebral disc has been reported to be innervated segmentally, but anesthetic block of the paravertebral sympathetic trunks and the L2 spinal nerve can relieve discogenic low back pain. In the current study, the sensory innervation of the dorsal portion of the L5-L6 intervertebral disc was investigated, because the disc anatomically corresponds to the L4-L5 disc in humans, and the dorsal portion of the human L4-L5 disc is frequently subject to injury that causes low back pain. METHODS: A retrograde transport of Fluoro-Gold (F-G; Fluorochrome, Denver, CO) was used. Subjects included nontreated control (n = 32) and sympathectomized rats in which paravertebral sympathetic trunks were removed from L2 to L3 (n = 9). In a ventral approach, Fluoro-Gold crystals were placed on the dorsal portion of the L5-L6 disc, and labeled neurons in the bilateral dorsal root ganglia from T10 to L6 were counted. RESULTS: Fluoro-Gold crystals did not leak from the dorsal portion of the L5-L6 disc in 14 of the 32 nontreated rats and in 5 of the 9 sympathectomized rats. These rats were used for analysis. Fluro-Gold-labeled neurons were found in dorsal root ganglia from T13 to L6 in the 14 control rats but only from L2 to L6 in the 5 sympathectomized rats. CONCLUSION: The dorsal portion of the L5-L6 disc of rats was shown to be multisegmentally innervated by the T13 to L6 dorsal root ganglia. The sensory fibers from T13, L1, and L2 dorsal root ganglia were shown to innervate the dorsal portion of the L5-L6 disc through the paravertebral sympathetic trunks. In contrast, those from the L3-L6 dorsal root ganglia may innervate the dorsal portion of the L5-L6 disc through the sinuvertebral nerves.

Animals↗
PubMed2001

Sensory innervation of the cervical facet joints in rats.

STUDY DESIGN: With a retrograde neurotracing method with Fluoro-Gold (FG; Fluorochrome, Denver, CO), the level of dorsal root ganglions (DRGs) innervating the C1-C2, C3-C4, and C5-C6 facet joints and their pathways were investigated in rats. OBJECTIVES: To clarify the levels of DRGs and parasympathetic nodose ganglions innervating the cervical facet joints and to determine the pathways from the facet joint to DRGs. SUMMARY OF BACKGROUND DATA: Patients with cervical facet lesions and whiplash sometimes experience diffuse neck pain, headache, arm, and shoulder pain, but the pattern of sensory innervation of the facet joint is still unclear. METHODS: Sixty male Sprague-Dawley rats were used. Fluoro-gold crystals (FG) were applied into the C1-C2 (C1-C2 group), C3-C4 (C3-C4 group) and C5-C6 (C5-C6 group) facet joints, and numbers of the labeled neurons in DRGs from C1 to T5 and nodose ganglions were determined. To determine the sensory pathway, bilateral sympathectomy was performed. RESULTS: Neurons labeled with FG were present in the DRGs from C1 through C8 in the C1-C2 group, from C1 to T2 in the C3-C4 group, and from C3 to T3 in the C5-C6 group without sympathectomy. In the nodose ganglions, 17 FG-labeled neurons were present. The number of the labeled neurons after sympathectomy was not significantly different in the C1, C2, and C3 DRGs in the C1-C2 group, in the C3 and C4 DRGs in the C3-C4 group, and in the C5 and C6 DRGs in the C5-C6 group from that in the groups without sympathectomy. In contrast, the number of labeled neurons in the DRGs was significantly less at the other levels than that in the groups without sympathectomy (P < 0.01). CONCLUSION: Sensory nerve fibers of the cervical facet joint were derived from the C1-T3 DRGs. Some sensory nerves from the cervical facet joint entered the paravertebral sympathetic trunks and reached the DRGs at multisegmental levels. The present findings regarding the multisegmental innervation to the facet joint may be of importance in the treatment of facet joint syndrome.

Animals↗
PubMed2001

Phenotypic inflammation switch in rats shown by calcitonin gene-related peptide immunoreactive dorsal root ganglion neurons innervating the lumbar facet joints.

STUDY DESIGN: The changes in dorsal root ganglion neurons innervating the L5-L6 facet joint were studied using the retrograde neurotransport method and the immunohistochemistry of calcitonin gene-related peptide in an inflammatory model of rats. OBJECTIVES: To determine by inflammatory stimulation the changes in calcitonin gene-related peptide-immunoreactive dorsal root ganglion neurons innervating the L5-L6 facet. SUMMARY OF BACKGROUND DATA: The rat L5-L6 facet joint is innervated from L1-L5 dorsal root ganglia. The presence of calcitonin gene-related peptide-immunoreactive dorsal root ganglion neurons innervating the L5-L6 facet joint has been confirmed, but the changes in the number and distribution of these neurons caused by inflammation have not been studied. METHODS: Retrograde transport of fluorogold was used in 20 rats: 10 in the control group and 10 in the inflammatory group. Using the dorsal approach, fluorogold crystals were injected into the left L5-L6 facet joint. Then 5 days after application, complete Freund's adjuvant (50 microg Mycobacterium butyricum in oil saline emulsion) was injected into the same L5-L6 facet joint (inflammatory group). Of the total fluorogold-labeled dorsal root ganglion neurons from T13-L6, the number and cross-sectional area of the cell profiles of fluorogold-labeled, calcitonin gene-related peptide-immunoreactive neurons in the bilateral dorsal root ganglia of both groups were evaluated. RESULTS: Fluorogold-labeled neurons were distributed throughout the ipsilateral dorsal root ganglia from L1-L5 in both groups. Of the fluorogold-labeled neurons, the ratios of the calcitonin gene-related peptide-immunoreactive L1, L2, L3, L4, and L5 dorsal root ganglion neurons, respectively, were 17%, 24%, 44%, 56%, and 50% in the control group and 50%, 39%, 51%, 61%, and 56% in the inflammatory group. The ratios of the calcitonin gene-related peptide-immunoreactive L1 and L2 dorsal root ganglion neurons labeled by fluorogold were significantly higher in the inflammatory group than in the control group (P < 0.05). The mean cross-sectional area of fluorogold-labeled, calcitonin gene-related peptide-immunoreactive cells from L1-L5 dorsal root ganglia increased from 621 +/- 64 microm2 to 893 +/- 63 microm2 in the inflammatory group (P < 0.01). CONCLUSIONS: The ratio of fluorogold-labeled, calcitonin gene-related peptide-immunoreactive neurons was significantly higher in the L1 and L2 dorsal root ganglia of the inflammatory group than in those of the control group, and the average cross-sectional area of the cells from L1-L5 dorsal root ganglion increased. Associated with the inflammation in the facet joints, the change in calcitonin gene-related peptide-immunoreactive neuron distribution and the phenotypic switch to large neurons may complicate the mechanism of facet joint inflammatory pain.

Animals↗
PubMed2001

Primary sensory neurons with dichotomizing axons projecting to the facet joint and the sciatic nerve in rats.

STUDY DESIGN: Dorsal root ganglion (DRG) neurons that have dichotomizing axons to the lumbar facet joint and to the sciatic nerve were investigated in rats using a double fluorescent labeling technique. OBJECTIVES: To clarify the existence of DRG neurons with dichotomizing axons projecting to the lumbar facet joint and to the sciatic nerve in rats. SUMMARY OF BACKGROUND DATA: DRG neurons having dichotomizing axons have been reported in several species and are considered to be related to referred pain. However, such DRG neurons have not been investigated in the lumbar spine. Clinically, pain from the lumbar facet joint is sometimes referred to the lower extremities innervated by the sciatic nerve. METHODS: Two kinds of neurotracers (DiI and FG) were used in the present double-labeling study. DiI crystals were placed in the left L5-L6 facet joint, and FG was applied to the ipsilateral sciatic nerve or along the midline of the L5 dermatome. Bilateral DRGs T13-S1 were observed by fluorescence microscope. RESULTS: DRG neurons double labeled with DiI and FG were recognized only in the ipsilateral DRGs from L3 to L6 levels. Approximately 3% of DRG neurons innervating the L5-L6 facet joint had other axons to the sciatic nerve. By contrast, no double-labeled neurons were observed after FG was applied to the L5 dermatome. CONCLUSIONS: In rats approximately 3% of DRG neurons innervating the lumbar facet joints have dichotomized axons projecting to the sciatic nerve.

Animals↗
PubMed2004

Innervation of the lumbar intervertebral disc by nerve growth factor-dependent neurons related to inflammatory pain.

STUDY DESIGN: We used anatomic tracers and immunoreactivity in rats to define dorsal root ganglion neuron populations innervating the lumbar discs in physiologic and inflammatory states. OBJECTIVES: To investigate the percentages of calcitonin gene-related peptide-immunoreactive (CGRP-ir) and isolectin B4 (IB4)-binding neurons innervating lumbar discs. SUMMARY OF BACKGROUND DATA: Small neurons are classified into two types. One contains CGRP and expresses the nerve growth factor receptor. The other binds IB4 and expresses the glial cell line-derived neurotrophic factor receptor. METHODS: A neurotracer, Fluoro-Gold, was applied to the L5-L6 disc in rats. Five days later, 50-microL saline (control group: n = 8) or Complete Freund's adjuvant (inflammatory group: n = 8) was applied to the disc. Seven days after the second operation, T13-L5 dorsal root ganglions were processed for double staining of CGRP and IB4. RESULTS: Of the Fluoro-Gold-labeled neurons, 50.1 +/- 4.6% (mean +/- SEM) were positive for CGRP and 0.7 +/- 0.6% positive for IB4 in the control group, while 65.6 +/- 4.7% were positive for CGRP and 1.0 +/- 1.0% positive for IB4 in the inflammatory group. The percentage of CGRP-ir neurons was significantly higher than that of IB4-binding neurons in both groups (P < 0.001, each). The percentage of CGRP-ir neurons in the inflammatory group was significantly higher than in the control group (P < 0.05). CONCLUSIONS: We found that most small neurons innervating the disc were CGRP-ir. Furthermore, disc inflammation caused an increase in CGRP-ir neurons but not IB4-binding neurons, suggesting that CGRP-ir, nerve growth factor-dependent neurons are more responsible for discogenic pain.

Animals↗
PubMed2004

Disc inflammation potentially promotes axonal regeneration of dorsal root ganglion neurons innervating lumbar intervertebral disc in rats.

STUDY DESIGN: The expression of growth-associated protein 43 (GAP-43), a marker of axonal growth, in the dorsal root ganglion (DRG) neurons innervating the lumbar intervertebral disc was assessed using the retrograde tracing method and immunohistochemistry. OBJECTIVES: To study whether disc inflammation affects GAP-43 expression in DRG neurons innervating the disc in rats. SUMMARY AND BACKGROUND DATA: Persistent inflammation and nerve ingrowth into the inner layer of degenerated discs can be a cause of discogenic pain. Although the presence of GAP-43-expressing nerve fibers in painful discs has been reported, the expression of GAP-43 in DRG neurons innervating the disc has not been studied. METHODS: Seven days after the application of Fluoro-Gold to the L5-L6 disc, 50 microL of saline (n = 10, control group) or complete Freund's adjuvant (n = 10, inflammatory group) was applied to the disc in rats. Ten days after the Fluoro-Gold application, T13-L5 DRGs were double-stained with GAP-43 and either calcitonin gene-related peptide or isolectin B4 (IB4). RESULTS: The percentage of Fluoro-Gold-labeled neurons that were positive for GAP-43 was significantly higher in the inflammatory group (44%) than in the control group (24%, P < 0.001). In both groups, the majority of GAP-43-positive neurons were small and positive for calcitonin gene-related peptide but not IB4. CONCLUSIONS: The present results suggest that disc inflammation potentially promotes axonal growth of DRG neurons innervating the disc. In light of the strong correlation between the expression of calcitonin gene-related peptide and nerve growth factor receptor, it is most likely that nerve growth factor-sensitive DRG neurons extend their axons following disc inflammation.

Animals↗
PubMed2006

Exposure of the nucleus pulposus to the outside of the anulus fibrosus induces nerve injury and regeneration of the afferent fibers innervating the lumbar intervertebral discs in rats.

STUDY DESIGN: Using a retrograde tracing method and immunohistochemistry, we assessed the expression of activating transcription factor 3 (ATF3), a marker of nerve injury, and growth-associated protein 43 (GAP-43), a marker of axonal growth, in dorsal root ganglion (DRG) neurons innervating the lumbar intervertebral discs in rats. OBJECTIVES: To investigate ATF3 and GAP-43 expression in DRGs innervating the intervertebral discs after exposure of the nucleus pulposus to the outside of the anulus fibrosus. SUMMARY OF BACKGROUND DATA: Degeneration of lumbar intervertebral discs is considered as a cause of low back pain. We speculated that exposure of the nucleus pulposus to the outside of the anulus fibrosus may induce nerve injury and ingrowth into the disc. METHODS: A neurotracer, Fluoro-Gold (F-G), was applied to the ventral aspect of L5-L6 intervertebral discs in 20 rats. The rats were classified into 2 groups: an NP group whose disc was punctured to expose the nucleus pulposus (n = 10) and a sham-operated group whose anulus fibrosus surface was scratched superficially (n = 10). Ten days after surgery, bilateral L1-L5 DRGs were processed for staining of ATF3 and GAP-43. RESULTS: In the NP group, 13.9% +/- 2.9% of the F-G-labeled neurons innervating the discs were positive for ATF3, while 19.3% +/- 2.7% were positive for GAP-43. In contrast, in the sham-operated group, only 0.8% +/- 0.4% of the F-G-labeled neurons were positive for ATF3 while 7.4% +/- 1.7% were positive for GAP-43. The percentage of both ATF3-immunoreactive (IR) and GAP-43-IR neurons in the NP group was significantly higher than in the sham-operated group (P < 0.05). CONCLUSIONS: ATF3-IR and GAP-43-IR neurons were significantly increased in the NP group. These results suggested that exposure of the nucleus pulposus to the outside of the anulus fibrosus induced nerve injury and in growth into the discs. These findings may explain discogenic lower back pain in patients with lumbar disc degeneration.

Activating Transcription Factor 3↗
PubMed2005

Axotomized bulbospinal neurons express c-Jun after cervical spinal cord injury.

In several central nervous system neuronal populations, axotomy triggers the upregulation of regeneration-associated genes such as c-Jun, which determines neurons ability to regenerate axon in a growth-permissive environment. We analyzed the expression of c-Jun in rat ventral medullary neurons after cervical hemisection in order to investigate their intrinsic regenerative potential. Maximal expression of c-Jun was observed 7 days after injury mainly in axotomized medullary neurons located in the gigantocellularis nucleus, the raphe nucleus and, although less intensively, in the rostral ventral respiratory group. This suggests that after high cervical injury, a large number of medullary neurons projecting to the spinal cord become competent for axonal regeneration, although this regenerating potential may not be equivalent between the various neuronal populations.

Animals↗
PubMed2006

Pituitary adenylate cyclase-activating polypeptide neurons of the ventromedial hypothalamus project to the midbrain central gray.

The pituitary adenylate cyclase-activating polypeptide (PACAP) and brain-derived neurotrophic factor (BDNF) neurons have recently been established as markers of the ventromedial hypothalamic nucleus (VMH). However, their neural projections from the VMH remained unknown. We examined whether PACAP and BDNF neurons in the VMH connected to the mesencephalic central gray (MCG), using the combination of in-situ hybridization and immunohistochemical tracing of Fluorogold (FG) injected into the MCG. Approximately 49% of PACAP neurons and 19% of BDNF neurons in the VMH contained the retrograde-transported FG, and 52% of FG-positive cells were PACAP neurons. These results indicate that a large number of PACAP neurons and a small number of BDNF neurons of the VMH project to the MCG.

Animals↗