Basal lamina formation at the site of spinal cord transection

Feringa, Earl R.; Kowalski, Timothy F.; Vahlsing, H. Lee

doi:10.1002/ana.410080204

Cited by 27 publications

(15 citation statements)

References 13 publications

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“…Regrowing postcommissural fornix axons arrest abruptly in close proximity to the BM deposits in the lesion centre, but continue to elongate when the BM is reduced. Our findings are in line with (i) in-vitro studies showing contact inhibition of axonal elongation by adult scar explants with large amounts of BM deposited around reactive astrocytes (Rudge & Silver, 1990) and (ii) in-vivo studies in spinal cord showing that regrowing axons do not cross but rather turn back at lesion-induced (Kao et al, 1977;Feringa et al, 1980) or implanted BM (Hausmann et al, 1996) and at pure collagen implants (Gelderd, 1990;Marchand & Woerly, 1990;Joosten et al, 1995), respectively.…”

Section: Role Of Bm In Regeneration Failuresupporting

confidence: 88%

“…Our findings are in line with (i) in‐vitro studies showing contact inhibition of axonal elongation by adult scar explants with large amounts of BM deposited around reactive astrocytes (Rudge & Silver 1990) and (ii) in‐vivo studies in spinal cord showing that regrowing axons do not cross but rather turn back at lesion‐induced (Kao et al . 1977;Feringa et al . 1980) or implanted BM (Hausmann et al .…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of collagen IV deposition promotes regeneration of injured CNS axons

Stichel

Hermanns

Luhmann

et al. 1999

Eur J of Neuroscience

154

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Scarring impedes axon regrowth across the lesion site and is one major extrinsic constraint to effective regeneration in the adult mammalian central nervous system. In the present study we determined whether specific biochemical or immunochemical modulation of one major component of the scar, the basal membrane (BM), would provide a means to stimulate axon regeneration in the mechanically transected postcommissural fornix of the adult rat. Basal membrane developed within the first 2 weeks after transection in spatiotemporal coincidence with the abrupt growth arrest of spontaneously regrowing axons. Local injection of anticollagen IV antibodies or alpha, alpha'-dipyridyl, an inhibitor of collagen triple helix formation and synthesis, significantly reduced lesion-induced BM deposition. This treatment allowed massive axon elongation across the lesion site. Anterograde tracing provided unequivocal evidence that regenerating axons follow their original pathway, reinnervate the appropriate target, the mammillary body, and become remyelinated with compact myelin. Presynaptic electrophysiological recordings of regenerated fibre tracts showed recovery to nearly normal conduction properties. Our results indicate that lesion-induced BM is an impediment for successful axonal regeneration and its reduction is a prerequisite and sufficient condition for regrowing axons to cross the lesion site.

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Section: Role Of Bm In Regeneration Failuresupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Inhibition of collagen IV deposition promotes regeneration of injured CNS axons

Stichel

Hermanns

Luhmann

et al. 1999

Eur J of Neuroscience

154

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“…Compared to pregelled bridges of SCs and Matrigel, this study demonstrated that initially fluid bridges promote both a robust increase in the elongation of astrocyte processes as well as the regeneration of brainstem axons into the transplant Early work with collagen matrices reported limited axon regeneration into pregelled compared to initially fluid transplants (36). The advantage of initially fluid transplants over pregelled ones may be i) in pregelled SC bridges, components in Matrigel, such as collagen type IV and laminin, may self-assemble into basal lamina (73) before transplantation and thereby contribute to a mesh-work of astrocyte processes similar to the glial limitans (23,24,40), and ii) fluid mixtures may rapidly conform to the surface of the cord stumps, thereby limiting the invasion of meningeal fibroblasts and inflammatory cells, analogous to duraplasty (30,31,82). The invasion of meningeal cells and their interaction with astrocytes creates glial limitans-like structures that may impede axonal growth (33,39,65).…”

Section: Discussionmentioning

confidence: 99%

Permissive Schwann Cell Graft/Spinal Cord Interfaces for Axon Regeneration

et al. 2015

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The transplantation of autologous Schwann cells (SCs) to repair the injured spinal cord is currently being evaluated in a clinical trial. In support, this study determined properties of spinal cord/SC bridge interfaces that enabled regenerated brainstem axons to cross them, possibly leading to improvement in rat hindlimb movement Fluid bridges of SCs and Matrigel were placed in complete spinal cord transections. Compared to pregelled bridges of SCs and Matrigel, they improved regeneration of brainstem axons across the rostral interface. The regenerating brainstem axons formed synaptophysin+ bouton-like terminals and contacted MAP2A+ dendrites at the caudal interface. Brainstem axon regeneration was directly associated with glial fibrillary acidic protein (GFAP+) astrocyte processes that elongated into the SC bridge. Electron microscopy revealed that axons, SCs, and astrocytes were enclosed together within tunnels bounded by a continuous basal lamina. Neuroglycan (NG2) expression was associated with these tunnels. One week after injury, the GFAP+ processes coexpressed nestin and brain lipid-binding protein, and the tips of GFAP+/NG2+ processes extended into the bridges together with the regenerating brainstem axons. Both brainstem axon regeneration and number of GFAP+ processes in the bridges correlated with improvement in hindlimb locomotion. Following SCI, astrocytes may enter a reactive state that prohibits axon regeneration. Elongation of astrocyte processes into SC bridges, however, and formation of NG2+ tunnels enable brainstem axon regeneration and improvement in function. It is important for spinal cord repair to define conditions that favor elongation of astrocytes into lesions/transplants.

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“…[63][64][65][67][68][69] Within the interstitial matrix of the adult brain the predominant ECM components are hyaluronan, hyaluronan-binding proteoglycans such as members of the aggrecan family, versican and brevican and glycoproteins such as members of the tenascin family. [66][67][68][70][71][72] During the development of the brain the molecular composition of the chondroitin-sulfate proteoglycans change dramatically to reflect the maturation of synaptic contacts 67,71 concomitant with a decreasing extracellular space that exists in the adult brain. 69,70,73,74 The extracellular space of the adult nervous system is not permissive for the type of proliferation and migration that occurs after an ischemic insult.…”

Section: Wound Healing In the Brainmentioning

confidence: 99%

Matrix Remodeling after Stroke: De Novo Expression of Matrix Proteins and Integrin Receptors

Ellison

Barone

Feuerstein

1999

Annals of the New York Academy of Sciences

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Following an ischemic insult to the central nervous system a reorganization of cells and tissue takes place as the surrounding cells attempt to limit the injury, repair the damage, and restore normal architecture of the brain. This tissue remodeling requires de novo synthesis of genes and proteins which enables cells to actively change their relationship with the existing extracellular matrix and with other cells to reorganize the damaged tissue. We have identified two key molecular components of the matrix remodeling process after focal ischemia: osteopontin (OPN) and its integrin receptor alpha v beta 3 (alpha v beta 3). OPN is initially expressed by activated macrophages and microglia in the periinfarct region (24-48 hr) and at later times (5-15 days) in the core infarct. After focal stroke the alpha v beta 3 was upregulated by astrocytes in the periinfarct region. Spatial and temporal analyses demonstrated that at 5 days after injury the alpha v beta 3-positive astrocytes were at a distance from the osteopontin-expressing macrophages; by 15 days the alpha v beta 3-expressing astrocytes were localized within an osteopontin-rich matrix. In vitro OPN was shown to induce migration of astrocytes in a Boyden chamber system. These data suggest that OPN derived from microglia at the infarct border zone (and possible macrophages in the infarct core) may serve as an "astrokine" (suggested term for astrocyte chemoattractant) to organize the astrocyte scar after focal stroke. Our data demonstrate profound changes in brain matrix remodeling after focal ischemic stroke, including the synthesis and release of matrix proteins alien to the normal brain, the expression of integrin receptors that ligate these proteins, and possibly a novel function for microglial-derived OPN in astrocyte migration after focal ischemia that may drive glial activation, organization, and repair functions.

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Basal lamina formation at the site of spinal cord transection

Cited by 27 publications

References 13 publications

Inhibition of collagen IV deposition promotes regeneration of injured CNS axons

Inhibition of collagen IV deposition promotes regeneration of injured CNS axons

Permissive Schwann Cell Graft/Spinal Cord Interfaces for Axon Regeneration

Matrix Remodeling after Stroke: De Novo Expression of Matrix Proteins and Integrin Receptors

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