Effects of fibrinolysis on neurite growth from dorsal root ganglia cultured in two‐ and three‐dimensional fibrin gels

The mechanism of neurite penetration of three‐dimensional fibrin matrices was investigated by culturing embryonic chick dorsal root ganglia (DRGs) within fibrin gels, upon fibrin gels, and upon laminin. The length of neurites within three‐dimensional matrices of fibrin was decreased in a concentration‐dependent manner by agents that inhibited plasmin, e.g., aprotinin, or that inhibited plasminogen activation, e.g., ϵ‐aminocaproic acid (EACA), or plasminogen antiserum. In contrast, such agents increased the length of neurites growing out from DRGs cultured upon two‐dimensional substrates of fibrin and had no effect on the length of neurites growing out from DRGs cultured upon laminin. Visualization of neurites within three‐dimensional fibrin matrices demonstrated that the distance between fibrin strands was much smaller than the diameter of neurites. All these data were consistent with the hypothesis that fibrinolysis localized to the region of the neurite tip is an important mechanism for neurite penetration of a physical barrier of fibrin strands arranged in a three‐dimensional matrix. © 1996 Wiley‐Liss, Inc.

[1]  S. Skaper,et al.  Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium. , 1980, Experimental cell research.

[2]  F. Grinnell,et al.  Fibroblast adhesion to fibrinogen and fibrin substrata: Requirement for cold-insoluble globulin (plasma fibronectin) , 1980, Cell.

[3]  S. Skaper,et al.  Molecular requirements for survival of cultured avian and rodent dorsal root ganglionic neurons responding to different trophic factors , 1982, Journal of neuroscience research.

[4]  B. Blombäck,et al.  Fibrin gel structure and clotting time. , 1982, Thrombosis research.

[5]  Göran Lundborg,et al.  Spatial‐Temporal progress of peripheral nerve regeneration within a silicone chamber: Parameters for a bioassay , 1983, The Journal of comparative neurology.

[6]  H. Fritz,et al.  Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. , 1983, Arzneimittel-Forschung.

[7]  S. Varon,et al.  Modification of fibrin matrix formation in situ enhances nerve regeneration in silicone chambers , 1985, The Journal of comparative neurology.

[8]  R. Lusskin,et al.  Evaluation and Therapy After Injury to Peripheral Nerves , 1986, Foot & ankle.

[9]  N. Seeds,et al.  Effect of proteases and their inhibitors on neurite outgrowth from neonatal mouse sensory ganglia in culture , 1986, Brain Research.

[10]  G. Moonen,et al.  Plasminogen activators in developing peripheral nervous system, cellular origin and mitogenic effect. , 1987, Brain research.

[11]  N. Danielsen,et al.  Exogenous matrix precursors promote functional nerve regeneration across a 15‐mm gap within a silicone chamber in the rat , 1987, The Journal of comparative neurology.

[12]  P. Knox,et al.  Role of plasminogen, plasmin, and plasminogen activators in the migration of fibroblasts into plasma clots , 1987, Journal of cellular physiology.

[13]  D. Monard.  Cell-derived proteases and protease inhibitors as regulators of neurite outgrowth , 1988, Trends in Neurosciences.

[14]  N. Seeds,et al.  Protease inhibitors influence the direction of neurite outgrowth. , 1989, Brain research. Developmental brain research.

[15]  H. Buettner,et al.  Neuronal plasminogen activators: cell surface binding sites and involvement in neurite outgrowth , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  R. Pittman,et al.  Neurite penetration into collagen gels requires Ca2+-dependent metalloproteinase activity. , 1989, Developmental neuroscience.

[17]  N. Kalderon.  Glial Plasminogen Activators in Developing and Regenerating Neural Tissue , 1990 .

[18]  P. Aebischer,et al.  The morphology of regenerating peripheral nerves is modulated by the surface microgeometry of polymeric guidance channels , 1990, Brain Research.

[19]  B. Seckel,et al.  Enhancement of peripheral nerve regeneration , 1990, Muscle & nerve.

[20]  G. Lundborg.  Nerve regeneration problems in a clinical perspective. , 1990, Restorative neurology and neuroscience.

[21]  J. Fawcett,et al.  The effects of protease inhibitors on axon growth through astrocytes. , 1990, Development.

[22]  D. Mosher.  Blood Coagulation and Fibrinolysis: An Overview , 1990, Clinical cardiology.

[23]  M. Kramer,et al.  Generation of cell surface-bound plasmin by cell-associated urokinase-type or secreted tissue-type plasminogen activator: a key event in melanoma cell invasiveness in vitro. , 1992, Experimental cell research.

[24]  N. Seeds,et al.  Plasminogen Activators and Plasminogen Activator Inhibitors in Neural Development a , 1992, Annals of the New York Academy of Sciences.

[25]  D. Sierra,et al.  Fibrin Sealant Adhesive Systems: A Review of Their Chemistry, Material Properties and Clinical Applications , 1993, Journal of biomaterials applications.