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G Raivich

Publications and source records attributed to G Raivich.

At least 55 records · Page 3Linked to original sources
PubMed1994

Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy.

There is increasing evidence that deprivation of the retrogradely transported neurotrophic protein nerve growth factor (NGF) accounts for some functional deficits known to occur in experimental diabetic neuropathy. Here we have studied changes in the axonal transport of endogenous NGF, NGF receptor (NGFR), and NGFR saturation (NGF/NGFR ratio) in the rat sciatic nerve after 2 months of streptozotocin (STZ)-induced diabetes mellitus. Compared with vehicle-treated control rats (blood glucose: 6-12 mM), there was a very clear reduction in the retrograde transport of NGF by 50% (P < 0.001) in STZ-treated, diabetic animals (blood glucose: 33-62 mM). No significant reduction in NGF axonal transport was observed in a subpopulation of STZ-treated rats (poor responders) with nearly normal glucose levels (range: 9-12 mM). No change was observed in any group in the retrograde transport of NGFR. Compared with control rats, however, the apparent NGFR saturation was reduced by 45% (P < 0.002) in STZ diabetics, whereas no change in NGFR saturation was observed in the STZ-poor responders. Moreover, the NGFR saturation and amount of retrogradely transported NGF were negatively correlated to the individual glucose concentration in diabetics (r2 = 0.47 and 0.55, respectively; P < 0.0001). These findings indicate that, while NGFR expression is normal in the STZ-diabetic neuropathy model, the marked decrease in receptor saturation observed in diabetics may reflect low peripheral NGF levels, which in consequence leads to the apparent deprivation of neuronal NGF in diabetic rats.

Animals↗
PubMed1994

Nerve growth factor: pathophysiological and therapeutic implications.

Neurotrophic factors are target-derived proteins capable of affecting survival, target innervation, and/or function of neuronal cell populations. Nerve growth factor (NGF) is the best-studied member of the genetic family called neurotrophins. There is however little knowledge whether other neurotrophins play a pathophysiological role in diseases of the peripheral and central nervous system. An increasing number of animal studies suggest that NGF plays a role in (a) peripheral nerve regeneration, (b) diabetic neuropathy, and (c) age-related neurodegenerative processes within the brain.

Animals↗
PubMed1993

Nerve growth factor and regeneration of peripheral nervous system.

Nerve growth factor, a well-known neurotrophic factor, supports the survival, differentiation and maintenance of sensory and sympathetic neurons during embryonic development and in the adult. This paper summarises the data on its involvement in peripheral nerve regeneration.

Animals↗
PubMed1993

Peripheral nerve regeneration: role of growth factors and their receptors.

Growth factors play a central role in the regulation of normal and injury-induced regenerative cell growth. The purpose of this article is to summarize the available data on the expression of different growth factors and their receptors in the injured peripheral nervous system and to discuss their possible role in promoting peripheral nerve regeneration.

Animals↗
PubMed1993

Quantitative immunohistochemistry in the rat facial nucleus with [125I]-iodinated secondary antibodies and in situ autoradiography: non-linear binding characteristics of primary monoclonal and polyclonal antibodies.

Indirect immunohistochemistry is an important routine method in histology and histopathology. Here we have investigated the quantitative aspects of antibody binding to tissue sections, using a range of monoclonal and polyclonal antibodies and the regenerating rat facial nucleus as the experimental model. The in situ binding of primary antibodies was quantified using appropriate [125I]-iodinated secondary antibodies and quantitative autoradiography. The majority of primary antibodies revealed an apparently bell-shaped curve of in situ antibody binding, with the binding increasing up to a specific antibody concentration and then decreasing; similar data were also obtained with enzymatic immunohistochemistry. There was also a close correlation between the quantitative changes in antibody binding during the time course of facial nerve regeneration and those observed with enzyme histochemistry.

Animals↗
PubMed1992

MHC-positive, ramified macrophages in the normal and injured rat peripheral nervous system.

Resident endoneurial macrophages form a prominent, but little recognized component of the PNS. We have studied immunocytochemically the distribution, morphology and immunophenotype of endoneurial macrophages in several normal peripheral nerves of the rat. In addition, we investigated the macrophage response following crush injury of the sciatic nerve. Resident endoneurial macrophages had a ramified morphology with processes oriented parallel to the long axis of nerve fibres. They were positive for several monocyte/macrophage markers such as ED1, ED2 and the recently-described MUC 101 and MUC 102 antibodies. They furthermore expressed the complement type three receptor, the CD4 antigen and MHC class I and II molecules. These results were consistent in all the peripheral nerves studied. In addition, 1000 rad of gamma-irradiation led to a strong reduction in the number of MHC class II-positive ramified cells in the peripheral nerves similar to that observed in other peripheral organs such as the heart. A considerable percentage of resident macrophages in the PNS and/or their precursor cells are therefore radiosensitive and could be related to the lineage of dendritic cells. Following crush injury, ED1-3-, OX-42-, MUC 101- and MUC 102-positive round macrophages were observed from 24 h postlesion onward at the site of trauma. In the distal part, they were observed to form strings of round, foamy macrophages probably involved in myelin phagocytosis. In contrast, the number of MHC class II-positive resident macrophages was only slightly increased at the site of trauma and in the distal part. These cells transformed from a ramified to a round morphology, but did not appear as typical strings of foamy macrophages. These results demonstrate that the PNS is provided with a resident macrophage population analogous in many respects to microglial cells in the CNS. These constitutively MHC class II-positive PNS microglial-like cells could act as the major antigen-presenting cells in the peripheral nerve. They may thus constitute a local immune defense system of the PNS with a function similar to that of microglial cells in the CNS.

Animals↗
PubMed1991

Vasoactive intestinal polypeptide in dorsal root terminals of the rat spinal cord is regulated by the axoplasmic transport in the peripheral nerve.

Vasoactive intestinal polypeptide (VIP) immunoreactivity in the upper spinal dorsal horn is markedly increased after transection, crush or vinblastine treatment of the ipsilateral, segmentally related peripheral nerve. After regeneration of the peripheral nerve, VIP disappears from the upper dorsal horn. Transection-induced VIP increase is abolished by rhizotomy. It is concluded that the expression of VIP is restricted by factor(s) carried by retrograde axoplasmic transport to dorsal root ganglion cells.

Animals↗
PubMed1991

The action of calcitonin gene-related peptide on astrocyte morphology and cyclic AMP accumulation in astrocyte cultures from neonatal rat brain.

The actions of calcitonin gene-related peptide (CGRP) were investigated on 9- to 14-day-old astrocyte cultures obtained from the cerebra of 1- to 2-day-old rats. The morphological appearance of the cells was monitored by immunofluorescent staining of glial fibrillary acidic protein (GFAP), and the concentration of adenosine 3',5'-monophosphate (cyclic AMP) was measured in the cultures using radioimmunoassay. CGRP induced a morphological change in cultured astrocytes from rat brain. Flat, polygonal cells positive for GFAP became multipolar with many processes. In addition, CGRP stimulated the accumulation of cyclic AMP by up to 30-fold, half maximal stimulation being obtained at CGRP concentrations in the range 100-300 nM. These data provide evidence for the presence of functional CGRP receptors on astrocytes and suggest a role for CGRP as an intercellular messenger controlling the state of differentiation and activation of astroglial cells.

Animals↗
PubMed1991

Increase of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor receptors in the regenerating rat facial nucleus.

Proliferation of microglial cells commonly occurs in the response of the central nervous system to injury, but little is known about how this process is regulated in vivo. Here we have studied the expression of receptors to macrophage colony-stimulating factor (MCSF) and granulocyte-macrophage colony-stimulating factor (GMCSF) in the normal and regenerating rat facial motor nucleus using receptor immunocytochemistry and in situ ligand binding methods. Under normal conditions, immunocytochemical staining with anti-MCSF receptor (MCSFR) antibody revealed a moderate but selective labelling of microglia-like cells of the facial motor nucleus. This immunostaining also colocalized with MUC102, a new monoclonal antibody raised against microglial cells in the rat central nervous system. Axotomy of the facial nerve led to a rapid increase in MCSFR-staining intensity 1 day after injury, which became maximal 7 days postoperatively and then decreased. A similar but somewhat slower increase was also observed for the specific [125I]MCSF binding with a maximum at 7 days. Specific [125I]GMCSF binding also increased, peaking at 4 days postoperatively and then rapidly decreasing to normal levels at 21 days after axotomy. In summary, axotomy of the facial nerve led to a rapid increase in receptors for MCSF and GMCSF, which coincided with the pattern of microglial proliferation in the regenerating facial motor nucleus. This apparent up-regulation of receptors for microglial growth factors may play an important role in preparing the microglia to participate in the cellular response to injury in the regenerating central nervous system.

Animals↗
PubMed1991

NGF receptor-mediated reduction in axonal NGF uptake and retrograde transport following sciatic nerve injury and during regeneration.

Injury to the rat sciatic nerve leads to the induction of nerve growth factor (NGF) receptors on the denervated Schwann cells and their disappearance on the regenerating axons of the axotomized, normally NGF-sensitive sensory and sympathetic neurons. This disappearance in the axonal expression and retrograde transport of NGF receptors is associated with a similarly dramatic reduction in the axonal uptake and retrograde transport of NGF following axotomy and during regeneration. In view of the massive NGF synthesis occurring in the injured nerve, these results suggest that, while sensory and sympathetic neurons are the primary targets of NGF in the normal peripheral nervous system, the denervated Schwann cells may become its primary target in the aftermath of nerve injury.

Animals↗
PubMed1991

A case for transmitter plasticity at the molecular level: axotomy-induced VIP increase in the upper spinal dorsal horn is related to blockade of retrograde axoplasmic transport of nerve growth factor in the peripheral nerve.

Blockade of retrograde axoplasmic transport in peripheral nerves, by means of perineurally applied microtubule inhibitors, results in an increased vasoactive intestinal polypeptide (VIP) reaction of the segmentally related, ipsilateral upper dorsal horn. Similar effect is elicited by the perineural application of an anti-Nerve Growth Factor (anti-NGF) serum. At the same time, both treatments result in depletion of Substance P from the same region of the spinal cord. It is assumed that this striking example of transmitter plasticity, obviously taking place at the molecular level, is due to a stimulating effect of NGF upon the perikaryal Substance P-synthesizing mechanism in dorsal root ganglion cells, and the inhibitory effect of NGF upon the VIP synthesizing machinery in these same nerve cells.

Animals↗
PubMed1989

Calcitonin gene-related peptide increases in rat facial motoneurons after peripheral nerve transection.

The rat facial nerve was transected and the retrograde reaction studied in the facial nucleus using light and electron microscopic immunohistochemistry and radioimmunoassay for calcitonin gene-related peptide (CGRP). An initial increase of CGRP-immunoreactivity (IR) was noted at 15 h after axotomy, thereafter CGRP-IR continued to rise to maximal levels around day 6 after which it gradually decreased and reached normal levels again after 5-6 weeks. Immunoreactive CGRP was found to fill the perikarya of facial motoneurons extending into dendrites and axons. Possible functional implications of CGRP as a neuroregulatory molecule during nerve regeneration are discussed.

Animals↗
PubMed1989

Increase of transferrin receptors and iron uptake in regenerating motor neurons.

After injury, motor neurons exhibit a number of metabolic and protein changes that are assumed to be part of an inherent neuronal regeneration program, which, when activated, eventually leads to functional restitution. The mechanisms underlying this regeneration are unclear, but it may be expected that factors supporting neuronal growth or survival play an important role in the restoration of neuronal integrity. A number of neuronal growth-associated proteins have been identified, but their functional roles remain unclear. This paper shows that axotomy results in a strong increase in transferrin receptors (TfRs) in regenerating motor neurons and that this phenomenon is functionally associated with an elevated uptake of exogenous iron. The association of TfR expression in regenerating motor neurons with direct uptake of iron into the brain provides evidence that iron uptake into neural tissue may be related to neuronal metabolic activation. We suggest that the enhanced capacity of regenerating motor neurons to bind transferrin and to take up iron plays an important role in neuronal repair.

Animals↗
PubMed1989

Topography of beta NGF receptor-positive and AChE-reactive neurons in the central nervous system.

Recent reports have led to widespread interest in the role of beta-nerve growth factor (beta NGF) in the central nervous system. To learn more about the action of beta NGF in the central nervous system we have mapped the distribution of beta NGF receptors and compared it with that of acetylcholinesterase (AChE), a sensitive enzyme marker for cholinergic neurons. In situ autoradiography revealed strong and saturable beta NGF binding to several groups of neurons in basal forebrain and brainstem. They also contain significant levels of mRNA coding for beta NGF receptors. beta NGF receptors and AChE are codistributed on the medial septal nuclei and in the basal forebrain, including the striatum. In the brainstem, beta NGF receptors are present on the neurons in the lower part of the reticular formation and in cochlear nuclei but do not correspond to the distribution of AChE reactivity.

Acetylcholinesterase↗