Passive immunization with tenascin-R (TN-R) polyclonal antibody promotes axonal regeneration and functional recovery after spinal cord injury in rats

You, Jian; Hong, Sun-Quan; Zhang, Maoying; Zhao, Hailin; Liu, Tianzhu; Zhou, Honglong; Cai, Yuchen; Xu, Zhimin; Guo, Yang; Jiang, Xiao-dan; Xu, Ran

doi:10.1016/j.neulet.2012.08.002

Cited by 8 publications

(6 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TN-C deficient animals subjected to hemisection in the lumbar spinal cord showed increased numbers of neurofilament-positive fibers along the hemisected edges of the spinal cord [ 188 ]. In contrast, deficiency of TN-R improves functional recovery of mice after compression of the thoracic spinal cord [ 189 ] with further studies using antibodies against TN-R showing improved recovery following SCI [ 190 ].…”

Section: Cspgs and Perineuronal Netsmentioning

confidence: 99%

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

2018

View full text Add to dashboard Cite

The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury.

show abstract

Section: Cspgs and Perineuronal Netsmentioning

confidence: 99%

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

2018

View full text Add to dashboard Cite

show abstract

“…Treatment with antibodies directed against an extracellular factor relies on blocking its function. Studies using antibodies against Nogo-A (Zhao et al, 2013) and TN-R (You et al, 2012) have shown improved recovery from spinal cord injury. In addition to the aforementioned strategies that rely on the elimination of ECM function, delivery of regeneration-promoting ECM-related molecules is possible.…”

Section: Extracellular Signals Influence Regeneration and Stem/progenmentioning

confidence: 99%

Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

Roll

Faissner

2014

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The limited regeneration capacity of the adult central nervous system (CNS) requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation. In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP) and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo. As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM), a complex network that contains numerous signaling molecules. It appears that signals in the damaged CNS lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C (TN-C). Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section.

show abstract

“…Accordingly, Yu et al indicated that an NgR vaccination (anti-NgR antibodies) can provide neuroprotection by inhibiting NgR function and other myelin-associated signalling factor inhibitors ( Yu et al, 2007 ) by upregulating proteins that might enhance regeneration and promote neuroprotection ( Teng and Tang, 2005 ). Moreover, combination strategies, such as neutralizing other inhibitors, cell transplantation, and neuroprotective approaches, will probably be more effective in promoting functional recovery after SCI with no side effects ( You et al, 2012 ). Similarly, in addition to Nogo-A and LINGO-1, tenascin-R (“TN-R″ axonal re-growth inhibitor belonging to TNs members), polyclonal antibodies have also been reported to upregulate at the lesion site of the injured spinal cord ( Deckner et al, 2000 ; Dityatev and Schachner, 2003 ; Woolf and Nogo, 2003).…”

Section: Cross-talk Between Neuronal Recovery and Capacity Of Neuroin...mentioning

confidence: 99%

“…Similarly, in addition to Nogo-A and LINGO-1, tenascin-R (“TN-R″ axonal re-growth inhibitor belonging to TNs members), polyclonal antibodies have also been reported to upregulate at the lesion site of the injured spinal cord ( Deckner et al, 2000 ; Dityatev and Schachner, 2003 ; Woolf and Nogo, 2003). Further studies evaluating the therapeutic potential of passive immunotherapy with specific TN-R polyclonal antibodies in acute SCI injury, have shown that local administration of TN-R antibodies at the lesion sites of the spinal cord-injured rats could potentially reduce the activity of RhoA and promote the functional recovery by promoting the axonal regrowth and functional recovery in some spinal cord-injured animals ( Apostolova et al, 2006 ; You et al, 2012 ). Accordingly.…”

Section: Cross-talk Between Neuronal Recovery and Capacity Of Neuroin...mentioning

confidence: 99%

Title: Immunotherapy; a ground-breaking remedy for spinal cord injury with stumbling blocks: An overview

Saeed¹

2023

Front. Pharmacol.

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a debilitating disorder with no known standard and effective treatment. Despite its ability to exacerbate SCI sequel by accelerating auto-reactive immune cells, an immune response is also considered essential to the healing process. Therefore, immunotherapeutic strategies targeting spinal cord injuries may benefit from the dual nature of immune responses. An increasing body of research suggests that immunization against myelin inhibitors can promote axon remyelination after SCI. However, despite advancements in our understanding of neuroimmune responses, immunoregulation-based therapeutic strategies have yet to receive widespread acceptance. Therefore, it is a prerequisite to enhance the understanding of immune regulation to ensure the safety and efficacy of immunotherapeutic treatments. The objective of the present study was to provide an overview of previous studies regarding the advantages and limitations of immunotherapeutic strategies for functional recovery after spinal cord injury, especially in light of limiting factors related to DNA and cell-based vaccination strategies by providing a novel prospect to lay the foundation for future studies that will help devise a safe and effective treatment for spinal cord injury.

show abstract

Passive immunization with tenascin-R (TN-R) polyclonal antibody promotes axonal regeneration and functional recovery after spinal cord injury in rats

Cited by 8 publications

References 34 publications

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

Title: Immunotherapy; a ground-breaking remedy for spinal cord injury with stumbling blocks: An overview

Contact Info

Product

Resources

About