Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers

doi:10.1016/0006-8993(84)91014-X

Brain Research

Volume 309, Issue 1, 20 August 1984, Pages 105-117

https://doi.org/10.1016/0006-8993(84)91014-X Get rights and content

Abstract

The outgrowth of neurites from cultured neurons can be induced by the extracellular matrix glycoproteins, fibronectin and laminin, and by polyornithine-binding neurite-promoting factors (NPFs) derived from culture media conditioned by Schwann, or other cultured cells. We have examined the occurrence of fibronectin, laminin and NPFs during peripheral nerve regeneration in vivo. A previously established model of peripheral nerve regeneration was used in which a transected rat sciatic nerve regenerates through a silicone chamber bridging a 10 mm interstump gap. The distribution of fibronectin and laminin during regeneration was assessed by indirect immunofluorescence. Seven days after nerve transection the regenerating structure within the chamber consisted primarily of a fibrous matrix which stained with anti-fibronectin but not anti-laminin. At 14 days, cellular outgrowths from the proximal and distal stumps (along which neurites grow) had entered the fibronectin-containing matrix, consistent with a role of fibronectin in promoting cell migration. Within these outgrowths non-vascular as well as vascular cell stained with anti-fibronectin and anti-laminin. Wihtin the degenerated distal nerve segment, cells characteristics of Bungner bands (rows of Schwann cells along which regenerating neurites extend) stained with anti-fibronectin and laminin. The fluid surrounding the regenerating nerve was found to contain NPF activity for cultured ciliary ganglia neurons which markedly increased during the period of neurite growth into the chamber. In previous studies using this particular neurite-promoting assay, laminin but to a much lesser extent fibronectin also promoted neurite outgrowth. Affinity-purified anti-laminin antibody failed to block chamber fluid NPF activity while completely blocking the neurite-promoting activity of laminin. These two results suggested that chamber fluid NPF activity did not consist of individual molecules of either fibronectin or laminin. The spatial and temporal distribution of insoluble fibronectin and laminin and the temporal correlation between chamber fluid NPF accumulation and neurite outgrowth support the possibility that these agents influence regenerative events including axonal elongation in vivo.

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Unlike the central nervous system, peripheral nerves can regenerate after injury. However, depending on the size of the lesion, the endogenous regenerative potential is not enough to replace the lost nerve tissue. Many strategies have been used to generate biomaterials capable of restoring nerve functions. Here, we set out to investigate whether adsorbing the extracellular matrix protein, laminin (LM), to poly-ℇ-caprolactone (PCL) filaments would enhance functional nerve regeneration. Initial in vitro studies showed that explants of dorsal root ganglia (DRGs) of P1 neonate mice exhibited stronger neuritogenesis on a substrate of LM that had been previously polymerized (polylaminin [polyLM]) than on ordinary LM. On the other hand, when silicone tubes filled with PCL filaments were used to bridge a 10-mm sciatic nerve gap in rats, only filaments coated with LM improved tissue replacement beyond that obtained with empty tubes. Motor function recovery correlated with tissue replacement as only LM-coated filaments consistently improved motor skills. Finally, analysis of the lateral gastrocnemius muscle revealed that the LM group presented twice the amount of α-bungarotixin–labeled motor plates. In conclusion, although polyLM was more effective in stimulating growth of sensory fibers out of DRGs in vitro, LM adsorbed to PCL filaments exhibited the best regenerative properties in inducing functional motor recovery after peripheral injury in vivo.
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Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers

Abstract

Brain Research

Develop. Biol.

Cell

Exp. Cell Res.

Develop. Biol.

Arch. Biochem. Biophys.

Develop. Biol.

J. Invest. Dermatol.

Cell

FEBS Lett.

Develop. Biol.

Exp. Cell Res.

Develop. Brain Res.

Meth. Enzymol.

J. Biol. Chem.

Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin

Cancer Res.

Nerve growth factor, laminin and fibronectin promote neurite growth in human fetal sensory ganglia cultures

J. Neurosci. Res.

Fibronectin promotes rat Schwann cell growth and motility

J. Cell Biol.

Identification, localization, and role of fibronectin in cultured bovine endothelial cells

Induction of neurite outgrowth by a conditioned-medium factor bound to the culture substratum

In vivo and in vitro observations on laminin produced by Schwann cells