Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury

被引:528
作者
Tysseling-Mattiace, Vicki M. [1 ,3 ]
Sahni, Vibhu [1 ,3 ]
Niece, Krista L. [4 ,5 ]
Birch, Derin [1 ,3 ]
Czeisler, Catherine [1 ,3 ]
Fehlings, Michael G. [6 ]
Stupp, Samuel I. [2 ,4 ,5 ]
Kessler, John A. [1 ,3 ]
机构
[1] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA
[2] Northwestern Univ, Dept Med, Chicago, IL 60611 USA
[3] Northwestern Univ, Inst Bionanotechnol Med, Chicago, IL 60611 USA
[4] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA
[5] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
[6] Univ Toronto, Dept Surg, Toronto, ON M5S 1A8, Canada
关键词
spinal cord injury; nanotechnology; gliosis; regeneration; extracellular matrix; functional recovery;
D O I
10.1523/JNEUROSCI.0143-08.2008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury ( SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.
引用
收藏
页码:3814 / 3823
页数:10
相关论文
共 30 条
[1]   MASCIS evaluation of open field locomotor scores: Effects of experience and teamwork on reliability [J].
Basso, DM ;
Beattie, MS ;
Bresnahan, JC ;
Anderson, DK ;
Faden, AI ;
Gruner, JA ;
Holford, TR ;
Hsu, CY ;
Noble, LJ ;
Nockels, R ;
Perot, PL ;
Salzman, SK ;
Young, W .
JOURNAL OF NEUROTRAUMA, 1996, 13 (07) :343-359
[2]   ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury [J].
Beattie, MS ;
Harrington, AW ;
Lee, R ;
Kim, JY ;
Boyce, SL ;
Longo, FM ;
Bresnahan, JC ;
Hempstead, BL ;
Yoon, SO .
NEURON, 2002, 36 (03) :375-386
[3]   Bridging areas of injury in the spinal cord [J].
Bunge, MB .
NEUROSCIENTIST, 2001, 7 (04) :325-339
[4]   Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice [J].
Bush, TG ;
Puvanachandra, N ;
Horner, CH ;
Polito, A ;
Ostenfeld, T ;
Svendsen, CN ;
Mucke, L ;
Johnson, MH ;
Sofroniew, MV .
NEURON, 1999, 23 (02) :297-308
[5]   Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys [J].
Crowe, MJ ;
Bresnahan, JC ;
Shuman, SL ;
Masters, JN ;
Beattie, MS .
NATURE MEDICINE, 1997, 3 (01) :73-76
[6]   Acute spinal cord injury, part I: Pathophysiologic mechanisms [J].
Dumont, RJ ;
Okonkwo, DO ;
Verma, RS ;
Hurlbert, RJ ;
Boulos, PT ;
Ellegala, DB ;
Dumont, AS .
CLINICAL NEUROPHARMACOLOGY, 2001, 24 (05) :254-264
[7]   Reactive astrocytes protect tissue and preserve function after spinal cord injury [J].
Faulkner, JR ;
Herrmann, JE ;
Woo, MJ ;
Tansey, KE ;
Doan, NB ;
Sofroniew, MV .
JOURNAL OF NEUROSCIENCE, 2004, 24 (09) :2143-2155
[8]   The glial scar and central nervous system repair [J].
Fawcett, JW ;
Asher, RA .
BRAIN RESEARCH BULLETIN, 1999, 49 (06) :377-391
[9]   Self-assembly and mineralization of peptide-amphiphile nanofibers [J].
Hartgerink, JD ;
Beniash, E ;
Stupp, SI .
SCIENCE, 2001, 294 (5547) :1684-1688
[10]   Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials [J].
Hartgerink, JD ;
Beniash, E ;
Stupp, SI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (08) :5133-5138