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Disruption of spinal cord white matter and sciatic nerve geometry inhibits axonal growth in vitro in the absence of glial scarring.

Pettigrew DB, Shockley KP, Crutcher KA - BMC Neurosci (2001)

Bottom Line: Neurite growth on uncrushed portions of spinal cord white matter or sciatic nerve was extensive and highly parallel with the longitudinal axis of the fiber tract but did not extend onto crushed portions.Moreover, neurite growth from neurons attached directly to crushed white matter or nerve tissue was shorter and less parallel compared with neurite growth on uncrushed tissue.Disruption of fiber tract geometry, perhaps involving myelin-associated neurite-growth inhibitors, may be sufficient to pose a barrier to regenerating axons in spinal cord white matter and peripheral nerves.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of Neurobiology and Anatomy University of Texas-Houston Health Science Center, USA. David.Pettigrew@uth.tmc.edu

ABSTRACT

Background: Axons within the mature mammalian central nervous system fail to regenerate following injury, usually resulting in long-lasting motor and sensory deficits. Studies involving transplantation of adult neurons into white matter implicate glial scar-associated factors in regeneration failure. However, these studies cannot distinguish between the effects of these factors and disruption of the spatial organization of cells and molecular factors (disrupted geometry). Since white matter can support or inhibit neurite growth depending on the geometry of the fiber tract, the present study sought to determine whether disrupted geometry is sufficient to inhibit neurite growth.

Results: Embryonic chick sympathetic neurons were cultured on unfixed longitudinal cryostat sections of mature rat spinal cord or sciatic nerve that had been crushed with forceps ex vivo then immediately frozen to prevent glial scarring. Neurite growth on uncrushed portions of spinal cord white matter or sciatic nerve was extensive and highly parallel with the longitudinal axis of the fiber tract but did not extend onto crushed portions. Moreover, neurite growth from neurons attached directly to crushed white matter or nerve tissue was shorter and less parallel compared with neurite growth on uncrushed tissue. In contrast, neurite growth appeared to be unaffected by crushed spinal cord gray matter.

Conclusions: These observations suggest that glial scar-associated factors are not necessary to block axonal growth at sites of injury. Disruption of fiber tract geometry, perhaps involving myelin-associated neurite-growth inhibitors, may be sufficient to pose a barrier to regenerating axons in spinal cord white matter and peripheral nerves.

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Comparisons of neurite growth on crushed and uncrushed sciatic nerve.A, The mean neurite length on crushed sciatic nerve was significantly less than that on uncrushed sciatic nerve. B, The mean angular deviation of neurites from an orientation parallel to the longitudinal axis of the underlying nerve was significantly greater on crushed nerve compared with that on uncrushed nerve. All bars indicate mean + SEM (**p < 0.0001).
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Figure 6: Comparisons of neurite growth on crushed and uncrushed sciatic nerve.A, The mean neurite length on crushed sciatic nerve was significantly less than that on uncrushed sciatic nerve. B, The mean angular deviation of neurites from an orientation parallel to the longitudinal axis of the underlying nerve was significantly greater on crushed nerve compared with that on uncrushed nerve. All bars indicate mean + SEM (**p < 0.0001).

Mentions: A similar quantification of neuronal density in relation to the crushed sciatic nerve showed that neuronal attachment was also significantly reduced (p < 0.001) on crushed sciatic nerve tissue (Fig. 5B). Since it is possible that the reduced neurite density on crushed sciatic nerve is a direct consequence of there being fewer neurons, a separate analysis was made comparing the lengths of neurites from neurons attached directly on crushed sciatic nerve with those attached on uncrushed sciatic nerve (Fig. 6A). Neurite length was significantly reduced on crushed sciatic nerve (p < 0.0001). To determine if the orientation of neurites is altered by crushed sciatic nerve tissue, the orientations of these neurites were also compared (Fig. 6B). The mean angular deviation of neurites from an orientation parallel to the longitudinal axis on crushed sciatic nerve was significantly greater than that of neurites on uncrushed sciatic nerve (p < 0.0001). Moreover, the variance of the deviation on crushed nerve was significantly greater than that on uncrushed nerve [F(65,122) = 3.226; p < 0.0001], indicating a wider range of orientations on crushed tissue.


Disruption of spinal cord white matter and sciatic nerve geometry inhibits axonal growth in vitro in the absence of glial scarring.

Pettigrew DB, Shockley KP, Crutcher KA - BMC Neurosci (2001)

Comparisons of neurite growth on crushed and uncrushed sciatic nerve.A, The mean neurite length on crushed sciatic nerve was significantly less than that on uncrushed sciatic nerve. B, The mean angular deviation of neurites from an orientation parallel to the longitudinal axis of the underlying nerve was significantly greater on crushed nerve compared with that on uncrushed nerve. All bars indicate mean + SEM (**p < 0.0001).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC32296&req=5

Figure 6: Comparisons of neurite growth on crushed and uncrushed sciatic nerve.A, The mean neurite length on crushed sciatic nerve was significantly less than that on uncrushed sciatic nerve. B, The mean angular deviation of neurites from an orientation parallel to the longitudinal axis of the underlying nerve was significantly greater on crushed nerve compared with that on uncrushed nerve. All bars indicate mean + SEM (**p < 0.0001).
Mentions: A similar quantification of neuronal density in relation to the crushed sciatic nerve showed that neuronal attachment was also significantly reduced (p < 0.001) on crushed sciatic nerve tissue (Fig. 5B). Since it is possible that the reduced neurite density on crushed sciatic nerve is a direct consequence of there being fewer neurons, a separate analysis was made comparing the lengths of neurites from neurons attached directly on crushed sciatic nerve with those attached on uncrushed sciatic nerve (Fig. 6A). Neurite length was significantly reduced on crushed sciatic nerve (p < 0.0001). To determine if the orientation of neurites is altered by crushed sciatic nerve tissue, the orientations of these neurites were also compared (Fig. 6B). The mean angular deviation of neurites from an orientation parallel to the longitudinal axis on crushed sciatic nerve was significantly greater than that of neurites on uncrushed sciatic nerve (p < 0.0001). Moreover, the variance of the deviation on crushed nerve was significantly greater than that on uncrushed nerve [F(65,122) = 3.226; p < 0.0001], indicating a wider range of orientations on crushed tissue.

Bottom Line: Neurite growth on uncrushed portions of spinal cord white matter or sciatic nerve was extensive and highly parallel with the longitudinal axis of the fiber tract but did not extend onto crushed portions.Moreover, neurite growth from neurons attached directly to crushed white matter or nerve tissue was shorter and less parallel compared with neurite growth on uncrushed tissue.Disruption of fiber tract geometry, perhaps involving myelin-associated neurite-growth inhibitors, may be sufficient to pose a barrier to regenerating axons in spinal cord white matter and peripheral nerves.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of Neurobiology and Anatomy University of Texas-Houston Health Science Center, USA. David.Pettigrew@uth.tmc.edu

ABSTRACT

Background: Axons within the mature mammalian central nervous system fail to regenerate following injury, usually resulting in long-lasting motor and sensory deficits. Studies involving transplantation of adult neurons into white matter implicate glial scar-associated factors in regeneration failure. However, these studies cannot distinguish between the effects of these factors and disruption of the spatial organization of cells and molecular factors (disrupted geometry). Since white matter can support or inhibit neurite growth depending on the geometry of the fiber tract, the present study sought to determine whether disrupted geometry is sufficient to inhibit neurite growth.

Results: Embryonic chick sympathetic neurons were cultured on unfixed longitudinal cryostat sections of mature rat spinal cord or sciatic nerve that had been crushed with forceps ex vivo then immediately frozen to prevent glial scarring. Neurite growth on uncrushed portions of spinal cord white matter or sciatic nerve was extensive and highly parallel with the longitudinal axis of the fiber tract but did not extend onto crushed portions. Moreover, neurite growth from neurons attached directly to crushed white matter or nerve tissue was shorter and less parallel compared with neurite growth on uncrushed tissue. In contrast, neurite growth appeared to be unaffected by crushed spinal cord gray matter.

Conclusions: These observations suggest that glial scar-associated factors are not necessary to block axonal growth at sites of injury. Disruption of fiber tract geometry, perhaps involving myelin-associated neurite-growth inhibitors, may be sufficient to pose a barrier to regenerating axons in spinal cord white matter and peripheral nerves.

Show MeSH
Related in: MedlinePlus