The p75 neurotrophin receptor is essential for neuronal cell survival and improvement of functional recovery after spinal cord injury

Neuroscience ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 668-682 ◽  
Author(s):  
G.K.T. Chu ◽  
W. Yu ◽  
M.G. Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Survival ◽  
Functional Recovery ◽  
Neuronal Cell ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Cord Injury

scholarly journals GSK-3 Inhibitor Promotes Neuronal Cell Regeneration and Functional Recovery in a Rat Model of Spinal Cord Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Fei Lei ◽  
Wen He ◽  
Xinggui Tian ◽  
Qingzhong Zhou ◽  
Lipeng Zheng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Glycogen Synthase ◽  
Neuronal Cell ◽  
Axon Growth ◽  
Competitive Inhibitor ◽  
Lower Limbs ◽  
Cell Regeneration ◽  
Cord Injury

The reparative process following spinal cord injury (SCI) is extremely complicated. Cells in the microenvironment express multiple inhibitory factors that affect axonal regeneration over a prolonged period of time. The axon growth inhibitory factor glycogen synthase kinase-3 (GSK-3) is an important factor during these processes. TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) is the most effective and specific non-ATP-competitive inhibitor of GSK-3. Here, we show that administering TDZD-8 after SCI was associated with significantly inhibited neuronal apoptosis, upregulated GAP-43 expression, increased density of cortical spinal tract fibers around areas of injury, and increased Basso, Beattie, and Bresnahan (BBB) scores in the lower limbs. These findings support the notion that GSK-3 inhibitors promote neuronal cell regeneration and lower limb functional recovery.

scholarly journals Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system

2003 ◽  
Vol 162 (2) ◽  
pp. 233-243 ◽  
Author(s):  
Catherine I. Dubreuil ◽  
Matthew J. Winton ◽  
Lisa McKerracher
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axon Growth ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Cord Injury ◽  
The Central Nervous System

Growth inhibitory proteins in the central nervous system (CNS) block axon growth and regeneration by signaling to Rho, an intracellular GTPase. It is not known how CNS trauma affects the expression and activation of RhoA. Here we detect GTP-bound RhoA in spinal cord homogenates and report that spinal cord injury (SCI) in both rats and mice activates RhoA over 10-fold in the absence of changes in RhoA expression. In situ Rho-GTP detection revealed that both neurons and glial cells showed Rho activation at SCI lesion sites. Application of a Rho antagonist (C3–05) reversed Rho activation and reduced the number of TUNEL-labeled cells by ∼50% in both injured mouse and rat, showing a role for activated Rho in cell death after CNS injury. Next, we examined the role of the p75 neurotrophin receptor (p75NTR) in Rho signaling. After SCI, an up-regulation of p75NTR was detected by Western blot and observed in both neurons and glia. Treatment with C3–05 blocked the increase in p75NTR expression. Experiments with p75NTR-null mutant mice showed that immediate Rho activation after SCI is p75NTR dependent. Our results indicate that blocking overactivation of Rho after SCI protects cells from p75NTR-dependent apoptosis.

scholarly journals P45 Forms a Complex with FADD and Promotes Neuronal Cell Survival Following Spinal Cord Injury

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69286 ◽  
Author(s):  
Tsung-Chang Sung ◽  
Zhijiang Chen ◽  
Sandrine Thuret ◽  
Marçal Vilar ◽  
Fred H. Gage ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Survival ◽  
Neuronal Cell ◽  
Cord Injury
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