Intrinsic neuronal and extrinsic glial determinants of axonal regeneration in the injured spinal cord

2009 ◽  
Vol 29 (47) ◽  
pp. 14881-14890 ◽  
Author(s):  
V. J. Tom ◽  
H. R. Sandrow-Feinberg ◽  
K. Miller ◽  
L. Santi ◽  
T. Connors ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Weiwei Zhang ◽  
Xiaoduo Zhan ◽  
Mingyong Gao ◽  
Audra D. Hamilton ◽  
Zhongying Liu ◽  
...  

The present study was designed to explore the therapeutic potential of self-assembling peptide nanofiber scaffold (SAPNS) delivered RhoA inhibitor to ameliorate the hostile microenvironment of injured spinal cord for axonal regeneration. After a transection was applied to the thoracic spinal cord of mice, the combination of SAPNS and CT04 (a cell permeable RhoA inhibitor), single SAPNS with vehicle, or saline was transplanted into the lesion cavity. Results showed that SAPNS+CT04 implants achieved the best therapeutic outcomes among treatment groups. The novel combination not only reconstructed the injured nerve gap but also elicited significant axonal regeneration and motor functional recovery. Additionally, the combination also effectively reduced the apoptosis and infiltration of activated macrophages in the injured spinal cord. Collectively, the present study demonstrated that SAPNS-based delivery of RhoA inhibitor CT04 presented a highly potential therapeutic strategy for spinal cord injury with reknitting lesion gap, attenuating secondary injury, and improving axonal regrowth.


2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Haruo Kanno ◽  
Damien D. Pearse ◽  
Hiroshi Ozawa ◽  
Eiji Itoi ◽  
Mary Bartlett Bunge

AbstractTransplantation of Schwann cells (SCs) is a promising therapeutic strategy for spinal cord repair. The introduction of SCs into the injured spinal cord has been shown to reduce tissue loss, promote axonal regeneration, and facilitate myelination of axons for improved sensorimotor function. The pathology of spinal cord injury (SCI) comprises multiple processes characterized by extensive cell death, development of a milieu inhibitory to growth, and glial scar formation, which together limits axonal regeneration. Many studies have suggested that significant functional recovery following SCI will not be possible with a single therapeutic strategy. The use of additional approaches with SC transplantation may be needed for successful axonal regeneration and sufficient functional recovery after SCI. An example of such a combination strategy with SC transplantation has been the complementary administration of neuroprotective agents/growth factors, which improves the effect of SCs after SCI. Suspension of SCs in bioactive matrices can also enhance transplanted SC survival and increase their capacity for supporting axonal regeneration in the injured spinal cord. Inhibition of glial scar formation produces a more permissive interface between the SC transplant and host spinal cord for axonal growth. Co-transplantation of SCs and other types of cells such as olfactory ensheathing cells, bone marrow mesenchymal stromal cells, and neural stem cells can be a more effective therapy than transplantation of SCs alone following SCI. This article reviews some of the evidence supporting the combination of SC transplantation with additional strategies for SCI repair and presents a prospectus for achieving better outcomes for persons with SCI.


1998 ◽  
Vol 9 (7) ◽  
pp. 681-711 ◽  
Author(s):  
S. Woerly ◽  
E. Pinet ◽  
L. De Robertis ◽  
M. Bousmina ◽  
G. Laroche ◽  
...  

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