Biomedical subjects

K Fried

Publications and source records attributed to K Fried.

At least 55 records · Page 3Linked to original sources

PubMed1995

TrkB-like immunoreactivity in trigeminal sensory nerve fibers of the rat molar tooth pulp: development and response to nerve injury.

The localization of TrkB, a signal transducing receptor for brain-derived neurotrophic factor and neurotrophin-4, was studied in the rat mandibular molar pulp during development and following nerve injury. Sections were incubated with rabbit polyclonal antiserum against the catalytic part of the TrkB receptor, thus only binding to full-length TrkB receptors, and examined by immunofluorescence microscopy and EM immunocytochemistry. At embryonic day 17, strongly TrkB-positive fibers were located in mandibular nerve trunks, in nerve fibers of deeper mesenchyme in close spatial relation to sites of future tooth development and in subepithelial nerve plexa. At postnatal days 1-12 intensely TrkB-positive nerve fibers surrounded and eventually invaded the developing dental papillae and pulps. In the normal adult pulp TrkB-immunoreactive axons were seen extending through the radicular pulp into the coronal areas. Double labelling demonstrated a considerable overlap between TrkB-like immunoreactivity and low affinity neurotrophin receptor-like immunoreactivity in the pulp, although some low affinity neurotrophin receptor-positive nerve fibers lacked TrkB-like immunoreactivity. Immunogold electron microscopy showed TrkB-like immunoreactivity in myelinated as well as in unmyelinated axons. One week following inferior alveolar nerve injury there was a dramatic decrease in the level of TrkB-like immunoreactivity labelling in the pulp, which paralleled an increase in the expression of Schwann cell low affinity neurotrophin receptor-like immunoreactivity. The first signs of regenerating TrkB-positive nerve fibers were found at 4 weeks post-operative, and at 9 weeks the distribution of pulpal TrkB-like immunoreactivity had returned to normal. These data indicate that brain-derived neurotrophic factor and/or neurotrophin-4 could be target-derived factors involved in sensory trigeminal tooth pulp nerve fiber development, differentiation or regeneration.

Aging↗

PubMed1995

Haemodynamic and immunohistochemical studies of rat incisor pulp after denervation and subsequent re-innervation.

The effects of injury to the inferior alveolar nerve on the distribution of neuropeptides and neurogenic blood-flow reactions were studied in rat mandibular dental pulp. In normal incisor pulps, calcitonin gene-related peptide (CGRP)-like immunoreactivity was common, while substance P- and neurokinin (NKA)-positive nerve fibres were much less abundant. There were no signs of vasoactive intestinal peptide-like, neuropeptide Y-like or 5-hydroxytryptamine-like immunoreactivity. In normal pulps, electrical stimulation (100 microA, 5 ms, 15 Hz for 30 s) of the tooth crown resulted in transient vasoconstriction followed by vasodilation, which was enhanced after alpha-adrenoceptor blockade. At 3 days-4 weeks after unilateral nerve section there were no signs of CGRP-, substance P- and NKA-immunoreactivity, and there was no vasodilation in response to tooth stimulation. The vasoconstrictor response was also absent during this period but at 4 weeks postoperatively a weak response was obtained and after 7 weeks the vasoconstrictor response had regained normal amplitude. At 7 weeks postoperatively, a large number of CGRP-positive fibres had reappeared and at 11 weeks the pattern of CGRP-immunoreactivity was normal. However, substance P- and NKA-immunoreactivity were not found at 7 or 11 weeks after surgery. Vasodilator responses appeared at 7 weeks, and showed normal amplitude at 11 weeks after the creation of the nerve lesion. The results show that during nerve regeneration, sympathetic vasoconstriction was regained earlier than neurogenic vasodilation in rat incisor teeth. The reappearance of neurogenic vasodilation after nerve injury was temporarily associated with the presence of CGRP-immunoreactivity in regenerating trigeminal afferent nerves.

Adrenergic alpha-Antagonists↗

PubMed1995

Teeth and tooth nerves.

(1) Although our knowledge on teeth and tooth nerves has increased substantially during the past 25 years, several important issues remain to be fully elucidated. As a result of the work now going on at many laboratories over the world, we can expect exciting new findings and major break-throughs in these and other areas in a near future. (2) Dentin-like and enamel-like hard tissues evolved as components of the exoskeletal bony armor of early vertebrates, 500 million years ago, long before the first appearance of teeth. It is possible that teeth developed from tubercles (odontodes) in the bony armor. The presence of a canal system in the bony plates, of tubular dentin, of external pores in the enamel layer and of a link to the lateral line system promoted hypotheses that the bony plates and tooth precursors may have had a sensory function. The evolution of an efficient brain, of a head with paired sense organs and of toothed jaws concurred with a shift from a sessile filter-feeding life to active prey hunting. (3) The wide spectrum of feeding behaviors exhibited by modern vertebrates is reflected by a variety of dentition types. While the teeth are continuously renewed in toothed non-mammalian vertebrates, tooth turnover is highly restricted in mammals. As a rule, one set of primary teeth is replaced by one set of permanent teeth. Since teeth are richly innervated, the turnover necessitates a local neural plasticity. Another factor calling for a local plasticity is the relatively frequent occurrence of age-related and pathological dental changes. (4) Tooth development is initiated through interactions between the oral epithelium and underlying neural crest-derived mesenchymal cells. The interactions are mediated by cell surface molecules, extracellular matrix molecules and soluble molecules. The possibility that the initiating events might involve a neural component has been much discussed. With respect to mammals, the experimental evidence available does not support this hypothesis. In the teleost Tilapia mariae, on the other hand, tooth germ formation is interrupted, and tooth turnover ceases after local denervation. (5) Prospective dental nerves enter the jaws well before onset of tooth development. When a dental lamina has formed, a plexus of nerve branches is seen in the subepithelial mesenchyme. Shortly thereafter, specific branches to individual tooth primordia can be distinguished. In bud stage tooth germs, axon terminals surround the condensed mesenchyme and in cap stage primordia axons grow into the dental follicle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Spinal axons in central nervous system scar tissue are closely related to laminin-immunoreactive astrocytes.

Although transected central nervous system axons fail to regrow after injuries in adult mammals, they send sprouts into the scar tissue that forms at the lesion. We have investigated the relation between scar cells, laminin-like immunoreactivity and cut spinal axons in two previously characterized spinal cord lesion types. Labeling with antisera to glial fibrillary acidic protein and laminin demonstrated that the scar tissue formed after lesions in the rat and cat dorsal and ventral funiculi showed prominent gliosis and strong laminin-like immunoreactivity four days to one year postlesion. Axonal sprouts in the scar, visualized with antibodies to neurofilament (RT97) or by tracing using fluorescein-conjugated dextran, were ensheathed by a thin layer of strongly laminin-immunoreactive tissue. Immunoelectron microscopy demonstrated that axons in the scar were ensheathed predominantly by astrocytes, and that the surface of the cells outlining the axons in the scar showed strong laminin-like immunoreactivity. Adhesive and neurite orienting properties in the scar tissue were assessed in an in vitro system where PC12 cells were cultured on spinal cord slices from dorsal funiculus-lesioned rats. Very few cells adhered to the spinal cord section except for the part where the scar tissue had formed, where numerous cells were attached. The PC12 cells that had adhered to the scar tissue were mainly seen in parts of the scar that showed laminin-like immunoreactivity and their neurites predominantly followed tissue showing laminin-like immunoreactivity. The close association between axonal sprouts and laminin-like immunoreactivity indicates a role for laminin in axonal growth and/or guidance in the injured spinal cord.

Animals↗

PubMed1995

Tubular ectasia of the rete testis: an ultrasound diagnosis.

Tubular ectasia of the rete testis is a rare benign entity that is often associated with some degree of obstruction at the epididymal level, either post-traumatic or postinfectious in nature. Its characteristic ultrasound findings have been well described in the radiologic literature. We report 6 cases of dilated rete testis diagnosed by ultrasound at our hospital over a 2-year period. Recognition of tubular ectasia by ultrasound, in the appropriate clinical setting, may eliminate unnecessary testicular biopsy or orchiectomy.

Aged↗

PubMed1995

Expression of the intermediate filament nestin during rodent tooth development.

The developing tooth represents a suitable model for understanding the molecular mechanisms involved in induction, morphogenesis and differentiation of organs. It is conceivable that the developmental changes could be reflected in the distribution of different cytoskeletal components and in this report we analyze the expression of the intermediate filament nestin during rodent tooth development at the protein and mRNA levels (by immuno light and electron microscopy, and by in situ hybridization). Nestin is expressed at all stages of tooth development, but the expression levels increase after birth in both ectodermal and ectomesenchymal derivatives. The shift in nestin distribution, from the proliferating dental lamina to the dental mesenchyme, indicates that nestin may be involved in inductive phenomena. At early stages of mineralization, nestin is seen within the apical parts of the presecretory ameloblasts. Nestin is also expressed in odontoblasts, both during odontogenesis and after tooth eruption. The increase in nestin expression from early to late developmental stages and sustained expression in a differentiated cell type contrasts with previously observed patterns of nestin expression during nerve and muscle development. This suggests that nestin could be used as a specific marker for the odontoblast.

Animals↗

PubMed1994

trkB-like immunoreactivity in rat dorsal root ganglia following sciatic nerve injury.

The expression of full-length trkB protein, the functional high affinity receptor for BDNF and NT-4, was examined by immunohistochemistry in adult rat L4-L5 dorsal root ganglia after different types of sciatic nerve lesions. In normal ganglia, 52.5% of the neurons showed trkB-like immunoreactivity. Size measurements demonstrated that trkB-like immunoreactivity was seen predominantly in small- and medium-sized cells. This was confirmed by the finding that 28% of all trkB-positive neurons showed affinity to RT97, an antibody which labels a neurofilament epitope specific for medium-sized and large primary afferent neurons. After crush, section or neuroma formation of the sciatic nerve, the proportion of trkB-positive cells was 64.5%, 58% and 61.9%, respectively. Since trkB-receptors are present in regenerating primary afferent neurons, these data could indicate that BDNF and/or NT-4 are involved in sensory nerve fiber regeneration after adult injury.

Animals↗

PubMed1994

trkC-like immunoreactivity in the primate descending serotoninergic system.

In the search for substances with a potential role in plastic responses of spinal motoneurons we have studied the distribution of trkC-like immunoreactivity in the spinal cord of adult monkeys (Macaca fascicularis). The presence of trkC, which is a signal-transducing receptor for neurotrophin-3, was detected by the use of indirect immunofluorescence with a rabbit polyclonal antibody raised against a synthetic peptide corresponding to the carboxy-terminal domain of the mouse trkC-encoded protein, thus detecting only full-length signal-transducing receptors. trkC-immunoreactive fibres/varicosities could be found at all spinal cord levels and the densest innervation was found in the autonomic intermediolateral and Onuf's nuclei, but somatic motoneuron pools also received a significant contribution of trkC-immunoreactive fibres. Terminals immunoreactive for trkC were also seen in the dorsal horn. Double-labelling experiments revealed a high degree of coexistence between trkC- and 5-hydroxytryptamine (serotonin)-like immunoreactivity in all areas except in the dorsal horn. The results of the present study suggest that neurotrophic signalling with an influence on serotoninergic as well as non-serotoninergic inputs to the adult monkey spinal cord is at hand.

Animals↗

PubMed1994

Substance P-, calcitonin gene-related peptide, growth-associated protein-43, and neurotrophin receptor-like immunoreactivity associated with unmyelinated axons in feline ventral roots and pia mater.

The spinal pia mater receives a rich innervation of small sensory axons via the ventral roots. Other sensory axons enter the ventral roots but end blindly or turn abruptly in hairpin loop-like formations and continue in a distal direction. In the present study, the content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, growth-associated protein (GAP-43)-, and low-affinity neurotrophin receptor protein (p75NGFr)-like immunoreactivity (-LI) associated with these different types of sensory axons was assessed with light and electron microscopic immunohistochemical techniques. In addition, the binding of antibodies against synthetic peptides representing unique sequences of residues in the products of the trk and trkB protooncogenes was analyzed. These genes encode membrane spanning proteins, which have been shown to constitute specific high affinity binding sites for several members of the nerve growth factor family of neurotrophic factors. The results of the present study imply that the ventral root afferents comprise several different types of sensory axons, which all contain SP-, CGRP-, GAP-43-, and p75NGFr-like immunoreactivities. In addition, at least some of the presumed sensory fiber bundles in ventral roots and the pia mater were immunoreactive for the trkB gene product. Moreover, leptomeningeal cells and nonneuronal cells of the ventral roots were shown to bind antibodies to both the trk and trkB gene products. The ventral root afferents seem to share their immunohistochemical pattern with pain-transducing axons at some other locations, such as the tooth pulp. The contents of SP- and CGRP-LI in sensory axons that reach the central nervous system (CNS) through the ventral root indicate that ventral root afferents may be involved in sensory mechanisms, such as the ventral root pain reaction, as well as in the control of the pial blood vessels. The demonstration of GAP-43 and neurotrophin receptor-immunoreactivities associated with unmyelinated fibers in ventral roots and the pia mater is discussed in relation to previous reports on postnatal plasticity in these axonal populations.

Animals↗

PubMed1994

Adhesive/repulsive properties in the injured spinal cord: relation to myelin phagocytosis by invading macrophages.

The vigorous ingrowth of cut CNS axons into peripheral nerve grafts indicates that the lack of neuronal regeneration within the brain and spinal cord cannot be explained merely by CNS neurons having an inherent weak regenerative capacity. Rather, the brain and spinal cord seem to contain molecules that inhibit axonal growth and, indeed, oligodendrocyte myelin has been demonstrated to effectively block nerve fiber growth. Macrophages can in vitro counteract this growth prohibitory property of the CNS. In this study we have examined the recruitment of macrophages and the removal of myelin in relation to neurite adhesive/repulsive properties in the injured spinal cord of adult rats. Cells immunoreactive for the macrophage-specific antibody ED1 rapidly invaded the lesion area after an incision in the dorsal or ventral funiculus. The number of macrophages remained high for several weeks in the scar tissue formed after both these injuries. This type of scar tissue has previously been reported to permit ingrowth and long-term persistence of axons. In the denervated area rostral to a dorsal funiculus transection, no or few ED1-immunoreactive cells were detected within the first month after the injury. However, at subsequent stages an increasing number of macrophages was found in this region. Myelin was removed much more rapidly at the site of the lesion than rostral to this (in the area undergoing Wallerian degeneration). In order to study adhesive/repulsive properties in the injured spinal cord in relation to local myelin content we employed an in vitro system in which PC12 cells were cultured on spinal cord slices. PC12 cells failed to adhere to sections from the intact spinal cord as well as to sections taken rostral to a dorsal funiculus transection, whereas many cells adhered to the glial scar formed at the lesion. Even at 15 months after the injury, very few PC12 cells attached to sections taken rostral to the transection despite the fact that no myelin could be detected in the denervated area at that time. These data suggest that, in addition to myelin-related growth inhibitory molecules, other factors may be involved in the failure of PC12 cells to adhere to the denervated spinal cord. Such factors could also affect axonal regrowth after spinal cord injury. The adhesion of PC12 cells to the lesion area may be a result of a locally high content of extracellular matrix molecules and/or cell adhesion molecules, factors which are not expressed in the region undergoing Wallerian degeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

trkC expression in the injured rat spinal cord.

Reactive non-neuronal cells express high levels of low-affinity neurotrophin receptor and truncated trkB receptors after spinal cord injury. Here we report that descending nerve fibres in the rat lateral spinal cord column show strong trkC-like immunoreactivity after traumatic spinal cord lesions in the adult rat. No change in trkC expression by glial cells could be detected by immunohistochemistry or in situ hybridization at the lesion site. The data suggest that regeneration of descending spinal cord axons could be encouraged by the trkC ligand, neurotrophin 3.

Animals↗

PubMed1993

Cat dental pulp after denervation and subsequent re-innervation: changes in blood-flow regulation and distribution of neuropeptide-, GAP-43- and low-affinity neurotrophin receptor-like immunoreactivity.

The effects of unilateral extramandibular inferior alveolar nerve injury on pulpal blood-flow responses to electrical stimulation and i.v. injections of substance P (SP) in cat mandibular canine teeth with a dentinal lesion were investigated with laser Doppler flowmetry. After blood-flow recordings, the teeth were fixed and the pulps were examined with light and electron microscopy. The distribution of pulpal SP, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), growth-associated protein (GAP-43) and low-affinity neurotrophin receptor (LANR)-like immunoreactivity was examined with immunohistochemical fluorescence microscopy. Blood-flow recordings, performed at 10 days and 1 month postoperatively, showed that vasodilation, occurring in control teeth after bipolar electrical stimulation of the tooth crown, was absent in the denervated pulps, whereas at 3 months, five of six teeth had regained responsiveness, although at a low level. There was enhanced vasodilation (by 370%) to SP injections (400 fmol i.v.) at 10 days in denervated pulps. Such supersensitivity was reduced at 1 month despite the apparent lack of nerve fibers, and the response fell further towards the level in control teeth at 3 months when pulpal axons reappeared. At 10 days and 1 month postoperatively, light and electron microscopy demonstrated that surgery had resulted in total pulpal denervation. At 3 and 6 months, a large number of regenerated pulpal axons reappeared, in accordance with previous findings. At 10 days and 1 month after nerve transection immunohistochemistry showed a complete loss of pulpal immunoreactivity to all the neuropeptides that were studied. At 3 and 6 months, neuropeptide immunoreactivity reappeared but far fewer number of pulpal nerve fibers were SP-, NKA- and CGRP-immunoreactive than under normal conditions, as demonstrated by double-labeling experiments with GAP-43- or LANR-antiserum. The results indicate that pulpal hemoregulatory functions, which are lost after denervation, do not return to normal levels after nerve regeneration. This malfunction may be caused by inadequate target re-innervation and/or a deficiency of neuropeptides in the re-innervated pulp.

Animals↗

PubMed1993

Characterization of glial trkB receptors: differential response to injury in the central and peripheral nervous systems.

In situ hybridization on sections from the adult rat peripheral and central nervous systems demonstrated that trkB mRNA was expressed not only by neurons but also by cells in central nervous system white matter as well as by Schwann cells in the sciatic nerve. In situ hybridization with an oligonucleotide complementary to the trkB tyrosine kinase domain could only demonstrate mRNA in neurons, indicating expression of truncated trkB receptors lacking the tyrosine kinase domain by glial cells. RNA blot analysis was performed on separately cultured central nervous system glial cells to study which cell types express trkB mRNA. Several transcripts encoding truncated trkB receptors were expressed at high levels in O-2A progenitors, astrocytes, and oligodendrocytes, but not trkB mRNA could be detected in microglia. The expression of trkB mRNA by glial cells in vivo was also investigated after injury; strongly elevated levels of mRNA encoding truncated receptors were detected in the glial scar formed after an incision in the spinal cord dorsal funiculus. In contrast, in the cut sciatic nerve, trkB mRNA decreased distal to the transection, and by 3 weeks only very low levels of mRNA could be detected. Immunoelectron microscopy located trkB-like immunoreactivity to axons and Schwann cells in the sciatic nerve. The expression of truncated trkB receptors by astrocytes, oligodendrocytes, and Schwann cells and the altered levels in response to injury indicate that glial trkB receptors may serve an important function in the intact and injured nervous system.

Animals↗

PubMed1993

Localization of NADPH-diaphorase activity in the dental pulp, periodontium and alveolar bone of the rat.

In this study we examined the presence and localization of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the dental pulp, periodontal tissues and alveolar bone of the rat. The presence of NADPH-d activity was also examined in cat pulp. The rat histochemical analysis revealed the presence of prominent NADPH-d activity both in cells of the sub-odontoblastic cell layer and in the odontoblasts, in the root as well as in the coronal pulp regions. In the pulpal horns, odontoblasts often had long processes with a high level of labelling indicating NADPH-d activity extending through the predentin and dentin. Moreover, endothelial cells of pulpal blood vessels were positive for NADPH-d in both species. However, no clearcut examples were found of pulpal nerve fibres positive for NADPH-d in the rat or cat and denervation performed in rats did not alter the enzyme staining patterns. In the periodontal tissue, NADPH-d activity was localized to cells on the alveolar bone surface of the periodontal ligament and, in addition, alveolar bone marrow crypts were filled with intensely labelled cells. In the gingival papillae, NADPH-d activity was observed in the basal cell layer of the epithelium. Endothelial cells of periodontal and gingival blood vessels showing positive staining for NADPH-d were occasionally noted.

Alveolar Process↗

PubMed1993

Close apposition among neighbouring axonal endings in a neuroma.

Axons in intact peripheral nerve trunks constitute independent afferent and efferent communication channels. However, when nerves are severed, several different forms of axon-axon cross-excitation develop in association with the injury site. In this study we have examined experimental sciatic nerve-end neuromas in rats with special interest in the compartmentalization of individual axons, and the barriers that separate close neighbours. At postinjury times at which functional coupling is known to occur, neuromas were found to contain many examples of axons in which adjacent membrane faces come into close contact without an intervening Schwann cell process. These occur in bundles containing from two to as many as 30 individual nerve fibres wrapped in a common Schwann cell sheath. The surface area of close apposition between axon pairs ranges up to several tens of micron2. Closely apposed axon profiles may be outgrowing branches of a single parent axon, but anterograde tracer data indicate that many belong to independent neurons. Closely apposed axons are separated from one another, and from associated Schwann cell processes, by a cleft about 130 A wide. No synapses, gap junctions or tight junctions were observed. Extracellular tracer studies using La3+ and Ruthenium Red indicated that the cleft system is patent, permitting the free diffusion of small molecules between the space adjacent to the axolemma and the bulk extracellular compartment. Together, these data provide a structural basis for interfibre interactions based on local electrical current flow (ephaptic crosstalk), as well as coupling mediated by K+ ions and neurotransmitter molecules.

Animals↗

PubMed1993

Distribution and axonal relations of macrophages in a neuroma.

After axotomy in the peripheral nervous system, most axons regrow and re-establish contact with their targets. Depending on the type of lesion, a varying number of nerve fibers fail to regenerate and terminate far from the target, forming a neuroma. Sensory axons trapped in a neuroma show abnormal sensitivity to various stimuli, and often fire spontaneously. In this study we have examined the distribution and axonal relations of macrophages in rat sciatic neuromas three days to one year after cutting and ligating the nerve. ED1-immunoreactive macrophages migrated into the neuroma in large numbers within the two first weeks after the injury. Most cells were at that time located 0.5-1 mm proximal to the ligature. From three weeks on, a majority of the ED1-immunoreactive cells contained numerous large vacuoles filled with myelin fragments. At sites of focal demyelination, macrophages often had direct contact with axonal membranes. At later survival stages (three months to one year) ED1-immunoreactive cells were seen not only in the area just proximal to the ligature, but also several millimeters proximal to this. Macrophages persisted in considerable numbers in the neuroma for at least one year. These data suggest that neuroma macrophages may participate in the genesis of electrophysiological abnormalities thought to underly chronic pain after neuroma formation, possibly by creating demyelinated axonal regions susceptible to external stimuli from e.g. neighboring nerve fibers, by releasing substances which influence regeneration and remodelling of axonal growth cones, or by direct actions on the denuded axonal membranes.

Animals↗

PubMed1993

Regrowth of motor axons following spinal cord lesions: distribution of laminin and collagen in the CNS scar tissue.

In previous studies we have demonstrated that spinal motoneurons in the adult cat can regenerate CNS-type axons through CNS scar tissue into denervated ventral roots. This scar tissue, which appears to support and sustain the growth of injured CNS axons, has been shown to have a persistent defect in the blood-brain barrier (BBB). In the present study, the binding of antibodies to nerve growth factor receptor (NGFr), laminin, collagen, and a microtubule associated protein (MAP5) was assessed with indirect immunohistochemical methods 4 days-20 weeks after a lesion in the ventral funiculus of the spinal cord. An increase in content of collagen-, laminin-, and NGFr-like immunoreactivity was observed in the scar tissue during the first 3 weeks. Although type I collagen dominated in superficial areas of the scar, type IV collagen and laminin-like immunoreactivity was observed in expanded perivascular spaces all over the lesion zone. Type IV collagen- and laminin-immunoreactive structures sometimes appeared to form strands which interconnected the ventral horn and the ventral root. Regenerating axons, as revealed by staining with MAP5 or NGFr antibodies, were observed in close association to these paths. It has been suggested that a breakdown of the BBB may play a vital role in certain types of CNS regeneration by increasing the access of blood-borne trophic factors to the lesion area. The demonstration of extracellular matrix proteins like laminin provides further evidence for the notion that the observed regenerative growth takes place in an environment that is markedly different from the normal CNS.

Animals↗

PubMed1993

Growth of ascending spinal axons in CNS scar tissue.

The aim of the present study was to test the capacity of spinal cord scar tissue to assist and sustain axon regrowth. In adult rats and cats the dorsal funiculus (DF) was cut at mid-thoracic or lumbar level, and a superficial incision in the DF rostral to the lesion was made in order to extend the penetrating lesion. Axonal tracing in rats 50-100 days postinjury with anterogradely transported wheatgerm agglutinin-conjugated horseradish peroxidase or rhodamine-conjugated dextran demonstrated that nerve fibers had entered the scar tissue. Axon ingrowth in the scar was further indicated by axonal immunoreactivity to the growth-associated protein GAP-43. The scar tissue showed low-affinity neurotropin receptor-like immunoreactivity in association with blood vessels and in the interstitium. The integrity of the blood-brain barrier in the extended dorsal funiculus lesion was disrupted for at least 11 months postinjury, assessed by i.v. injections of free HRP or Evans blue. The present study shows that penetrating injury in the dorsal funiculus produces a CNS environment permissive for axonal sprouting and that PNS influence is not necessary for spinal tract regrowth. A possible relationship between the absence of an intact BBB and injury-induced axonal sprouting is discussed.

Animals↗