Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro

Snow, Diane; Lemmon, Vance; Carrino, David A.; Caplan, Arnold I.; Silver, Jerry

doi:10.1016/s0014-4886(05)80013-5

Cited by 730 publications

(523 citation statements)

References 67 publications

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“…The rapid and long lasting upregulation of proteoglycans within the vicinity of the glial scar has implicated them in the creation of nonpermissive growth environments in the CNS, similar to their role in boundary formation within the CNS during development (Fitch and Silver, 1997b;Grimpe and Silver, 2004;Silver, 1994;Snow et al, 1990). It is now well established that proteoglycans associated with reactive astrocytes clearly inhibit neurite outgrowth in vitro (Bovolenta et al, 1993;Canning et al, 1993;Dou and Levine, 1994;McKeon, et al, 1991;Snow et al, 1990;Tom, et al, 2004b), and these molecules also appear to play a key role in creating an environment that is not appropriate for successful long-distance regeneration of adult neurons after injury in vivo, since their modification allows successful regeneration to occur (Bradbury et al, 2002;Houle et al, 2006;Steinmetz et al, 2005).…”

Section: Molecules Within the Glial Scar Contribute To Regenerative Fmentioning

confidence: 99%

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Fitch

Silver

2008

Experimental Neurology

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Spinal cord and brain injuries lead to complex cellular and molecular interactions within the central nervous system in an attempt to repair the initial tissue damage. Many studies have illustrated the importance of the glial cell response to injury, and the influences of inflammation and wound healing processes on the overall morbidity and permanent disability that result. The abortive attempts of neuronal regeneration after spinal cord injury are influenced by inflammatory cell activation, reactive astrogliosis and the production of both growth promoting and inhibitory extracellular molecules. Despite the historical perspective that the glial scar was a mechanical barrier to regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Unlike myelin associated inhibitory molecules, which remain at largely static levels before and after central nervous system trauma, inhibitory extracellular matrix molecules are dramatically upregulated during the inflammatory stages after injury providing a window of opportunity for the delivery of candidate therapeutic interventions. While high dose methylprednisolone steroid therapy alone has not proved to be the solution to this difficult clinical problem, other strategies for modulating inflammation and changing the make up of inhibitory molecules in the extracellular matrix are providing robust evidence that rehabilitation after spinal cord and brain injury has the potential to significantly change the outcome for what was once thought to be permanent disability.

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Section: Molecules Within the Glial Scar Contribute To Regenerative Fmentioning

confidence: 99%

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Fitch

Silver

2008

Experimental Neurology

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651

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Section: Introductionmentioning

confidence: 99%

“…In addition, the guidance properties of membrane-tethered molecules as well as the short-range action of secreted guidance molecules (such as Slits and Semaphorins) could be mimicked in vitro by this assay 17,18 . Also stripe assay experiments were conducted to unravel potential guidance properties of extracellular matrix components 19,20 and of cell adhesion molecules of the IgG superfamily 21 .Of note, the stripe assay was employed as an in vitro assay to investigate the navigation responses of both axonal growth cones toward guidance cues and of migrating cells 4,22,23 . With respect to the latter, neural crest cells 22 and oligodendrocytes 23,24 , but also non-neuronal cells such as tumor cells, have been studied 25 .…”

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confidence: 99%

Stripe assay to examine axonal guidance and cell migration

et al. 2007

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Stripe assays have been widely employed as in vitro test systems to study the responses of growing axons, as well as migrating cells, to established or novel guidance molecules. We provide detailed protocols for both the original and the modified version of this assay, as they allow the analysis of the 'guidance properties' of active components present in crude membrane fractions or as purified molecules. Silicon matrices are used to produce striped patterns of active molecules on a surface (referred to as 'carpet'), followed by culturing of neurons, or any other cell type, on these carpets. After 1-2 days in culture, striped outgrowth of extending neuritesindicative of guided migration of cell processes-can be observed. We also discuss potential other applications (e.g., in neuronal regeneration and development) and modifications of the assay. The preparation of 10-12 carpets takes approximately 4-5 h. INTRODUCTIONThe stripe assay was originally designed by F. Bonhoeffer and co-workers 1,2 in the late 1980s to analyze fundamental axonal guidance mechanisms governing the formation of the topographic map established in the chick retino-tectal system (for review, see ref.3). Employing this assay, the presence of a graded distribution of repulsive axon guidance cues, present predominantly in posterior tectal membranes, was discovered. Subsequently, this assay was modified, permitting the identification of ephrin-As as the key components present in posterior membranes that are responsible for the repulsive properties 4-7 .The stripe assay has since been used to uncover guidance cues and mechanisms in many principal neuronal projections, including, for example, the hippocampal, thalamic and olfactory systems [8][9][10][11] . The stripe assay was also applied to investigate neurite outgrowth and guidance behavior related to neuronal regeneration 12-15 and branch formation 16 . Furthermore, the stripe assay has proven valuable in dissecting signaling cascades initiated downstream of axonal guidance receptors activated by ligands printed in a striped pattern [12][13][14][15] . In addition, the guidance properties of membrane-tethered molecules as well as the short-range action of secreted guidance molecules (such as Slits and Semaphorins) could be mimicked in vitro by this assay 17,18 . Also stripe assay experiments were conducted to unravel potential guidance properties of extracellular matrix components 19,20 and of cell adhesion molecules of the IgG superfamily 21 .Of note, the stripe assay was employed as an in vitro assay to investigate the navigation responses of both axonal growth cones toward guidance cues and of migrating cells 4,22,23 . With respect to the latter, neural crest cells 22 and oligodendrocytes 23,24 , but also non-neuronal cells such as tumor cells, have been studied 25 .The assay allows assessment of guidance activity of established molecules and also testing potential guidance properties of hitherto uncharacterized molecules such as RGM, the Wnt signaling inhibitor SFRP1 or the morphogen Sonic h...

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“…also Orlino et al 2000 and was detected in the dorsal midline of the optic tectum in neonate hamsters (Snow et al 1990a) during the growth of retinal axons (Frost et al 1979), a population that must be prevented from crossing the midbrain midline. In a subsequent analysis employing nitrocellulose-coated culture dishes as a substratum to attach laminin (or N-CAM) and proteoglycans of interest, the behavior of the main target population -dorsal root ganglion (DRG) neurons -in explant cultures was evaluated and showed a general inhibitory effect of KS/CS-PGs, DS-PG and, in much smaller measure, of a chondrosarcoma tumor cell CS-PG, devoid of KS and predominantly 4-sulfated (Snow et al 1990b). It is interesting to notice that Dou and Levine (1995) showed subsequently that chondroitin 4-sulfate (CS-4), CS-6 and KS inhibit neurite outgrowth from both cerebellar and DRG neurons on laminin-coated surfaces whereas DS and HS had no effect on these neurons under similar conditions.…”

Section: Non-neuronal Cs/ks/dspgs Modulation Of Neurite Growth At Thementioning

confidence: 99%

Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

Cavalcante

Garcia-Abreu

Moura‐Neto

et al. 2002

An. Acad. Bras. Ciênc.

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Bilaterally symmetric organisms need to exchange information between the left and right sides of their bodies to integrate sensory input and to coordinate motor control. Thus, an important choice point for developing axons is the Central Nervous System (CNS) midline. Crossing of this choice point is influenced by highly conserved, soluble or membrane-bound molecules such as the L1 subfamily, laminin, netrins, slits, semaphorins, Eph-receptors and ephrins, etc. Furthermore, there is much circumstantial evidence for a role of proteoglycans (PGs) or their glycosaminoglycan (GAG) moieties on axonal growth and guidance, most of which was derived from simplified models. A model of intermediate complexity is that of cocultures of young neurons and astroglial carpets (confluent cultures) obtained from medial and lateral sectors of the embryonic rodent midbrain soon after formation of its commissures. Neurite production in these cocultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exerted an inhibitory or nonpermissive effect on neuritic growth that was correlated to a higher content of both heparan and chondroitin sulfates (HS and CS). Treatment with GAG lyases shows minor effects of CS and discloses a major inhibitory or non-permissive role for HS. The results are discussed in terms of available knowledge on the binding of HSPGs to interative proteins and underscore the importance of understanding glial polysaccharide arrays in addition to its protein complement for a better understanding of neuron-glial interactions.

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Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro

Cited by 730 publications

References 67 publications

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Stripe assay to examine axonal guidance and cell migration

Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

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