Basic techniques for long distance axon tracing in the spinal cord

2013 ◽  
Vol 76 (12) ◽  
pp. 1240-1249 ◽  
Author(s):  
Daniel J. Hellenbrand ◽  
Katie E. Kaeppler ◽  
Euhaa Hwang ◽  
Mark E. Ehlers ◽  
Ross D. Toigo ◽  
...  
2021 ◽  
Author(s):  
Wen Yin ◽  
Weiwei Xue ◽  
Hecheng Zhu ◽  
He Shen ◽  
Zhifeng Xiao ◽  
...  

Only the first scar tissue removal is a key time point for chronic complete SCI repair. Endogenous NSCs could be intensively activated after the first scar tissue removal and contribute to the chronic SCI repair after bio-scaffold implantation.


2008 ◽  
Vol 99 (1) ◽  
pp. 297-307 ◽  
Author(s):  
Salma S. Islam ◽  
Pavel V. Zelenin

Two forms of undulatory locomotion in the lamprey (a lower vertebrate) have been described earlier: fast forward swimming (FFS) used for long distance migrations and slow backward swimming (SBS) used for escape from adverse tactile stimuli. In the present study, we describe another form of escape behavior: slow forward swimming (SFS). We characterize the kinematic and electromyographic patterns of SFS and compare them with SBS and FFS. The most striking feature of SFS is nonuniformity of shape and speed of the locomotor waves propagating along the body: close to the site of stimulation, the waves slow down and the body curvature increases several-fold due to enhanced muscle activity. Lesions of afferents showed that sensory information critical for elicitation of SFS is transmitted through the dorsal roots. In contrast, sensory signals that induce SBS are transmitted through the dorsal roots, lateral line nerves, and trigeminal nerves. Persistence of SFS and SBS after different lesions of the spinal cord suggests that the ascending and descending pathways, necessary for induction of SBS and SFS, are dispersed over the cross section of the spinal cord. As shown previously, during FFS (but not SBS) the lamprey maintains the dorsal-side-up body orientation due to vestibular postural reflexes. In this study we have found that the orientation control is absent during SFS. The role of the spinal cord and the brain stem in generation of different forms of undulatory locomotion is discussed.


Neuron ◽  
2014 ◽  
Vol 83 (4) ◽  
pp. 789-796 ◽  
Author(s):  
Paul Lu ◽  
Grace Woodruff ◽  
Yaozhi Wang ◽  
Lori Graham ◽  
Matt Hunt ◽  
...  

Author(s):  
CS Ahuja ◽  
M Khazaei ◽  
P Chan ◽  
J Bhavsar ◽  
Y Yao ◽  
...  

Background: Human induced pluripotent stem cell-derived neural stem cells (hiPS-NSCs) represent an exciting therapeutic approach for traumatically spinal cord injury (SCI). Unfortunately, most patients are the in chronic injury phase where a dense perilesional chondroitin sulfate proteoglycan (CSPG) scar significantly hinders regeneration. CSPG-degrading enzymes can enhance NSC-mediated recovery, however, nonspecific intrathecal administration causes off-target effects. We aimed to genetically engineer hiPS-NSCs to express a scar-degrading ENZYME into their local environment to enhance functional recovery. Methods: A bicistronic scar-degrading ENZYME and RFP reporter vector was non-virally integrated into hiPS-NSCs and monoclonalized. ENZYME activity was assessed by WST-1 and DMMB biochemical assays and an in vitro CSPG spot assay with hiPS-NSC-derived neurons. To assess in vivo efficacy, T-cell deficient rats (N=60) with chronic (8wk) C6-7 SCIs were randomized to receive (1)SMaRT cells, (2)hiPS-NSCs, (3)vehicle, or (4)sham surgery. Results: SMaRT cells retained key hiPS-NSC characteristics while stably expressing ENZYME. The expressed ENZYME could appropriately degrade in vitro and ex vivo CSPGs. While blinded neurobehavioural and immunohistochemical assessments are ongoing at 40wks post-injury, an interim analysis demonstrated human cells extending remarkably long (≥20,000µm) axons along host white matter tracts. Conclusions: This work provides exciting proof-of-concept data that genetically-engineered SMaRT cells can degrade CSPGs and human NSCs can extend long-distance processes in chronic SCI.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Stuart I. Hodgetts ◽  
Jun Han Yoon ◽  
Alysia Fogliani ◽  
Emmanuel A. Akinpelu ◽  
Danii Baron-Heeris ◽  
...  

Ciliary neurotrophic factor (CNTF) promotes survival and enhances long-distance regeneration of injured axons in parts of the adult CNS. Here we tested whether CNTF gene therapy targeting corticospinal neurons (CSN) in motor-related regions of the cerebral cortex promotes plasticity and regrowth of axons projecting into the female adult F344 rat spinal cord after moderate thoracic (T10) contusion injury (SCI). Cortical neurons were transduced with a bicistronic adeno-associated viral vector (AAV1) expressing a secretory form of CNTF coupled to mCHERRY (AAV-CNTFmCherry) or with control AAV only (AAV-GFP) two weeks prior to SCI. In some animals, viable or nonviable F344 rat mesenchymal precursor cells (rMPCs) were injected into the lesion site two weeks after SCI to modulate the inhibitory environment. Treatment with AAV-CNTFmCherry, as well as with AAV-CNTFmCherry combined with rMPCs, yielded functional improvements over AAV-GFP alone, as assessed by open-field and Ladderwalk analyses. Cyst size was significantly reduced in the AAV-CNTFmCherry plus viable rMPC treatment group. Cortical injections of biotinylated dextran amine (BDA) revealed more BDA-stained axons rostral and alongside cysts in the AAV-CNTFmCherry versus AAV-GFP groups. After AAV-CNTFmCherry treatments, many sprouting mCherry-immunopositive axons were seen rostral to the SCI, and axons were also occasionally found caudal to the injury site. These data suggest that CNTF has the potential to enhance corticospinal repair by transducing parent CNS populations.


Cell ◽  
2012 ◽  
Vol 150 (6) ◽  
pp. 1264-1273 ◽  
Author(s):  
Paul Lu ◽  
Yaozhi Wang ◽  
Lori Graham ◽  
Karla McHale ◽  
Mingyong Gao ◽  
...  

2016 ◽  
Vol 36 (27) ◽  
pp. 7283-7297 ◽  
Author(s):  
M. Cheah ◽  
M. R. Andrews ◽  
D. J. Chew ◽  
E. B. Moloney ◽  
J. Verhaagen ◽  
...  

Physiology ◽  
1998 ◽  
Vol 13 (6) ◽  
pp. 294-298 ◽  
Author(s):  
Martin E. Schwab

Neurite growth and regeneration in the adult central nervous system (CNS) is extremely limited. An important factor contributing to these restrictions is specific growth inhibitory proteins associated with oligodendrocytes and CNS myelin. A major inhibitory factor is the antigen of a monoclonal antibody; the application of this neutralizing antibody to spinal cord- or brain-lesioned adult rats induces long-distance regeneration of lesioned axons, as well as a specific increase in sprouting and rewiring of the cortical output system to the brain stem and the spinal cord. These anatomic changes are paralleled by important functional recoveries of locomotion and precision movements.


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