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

doi:10.1016/j.neulet.2012.08.002

Neuroscience Letters

Volume 525, Issue 2, 13 September 2012, Pages 129-134

https://doi.org/10.1016/j.neulet.2012.08.002 Get rights and content

Abstract

Tenascin-R (TN-R) is a neural specific protein and an important molecule involved in inhibition of axonal regeneration after spinal cord injury (SCI). Here we report on rabbit-derived TN-R polyclonal antibody, which acts as a TN-R antagonist with high titer and high specificity, promoted neurite outgrowth and sprouting of rat cortical neurons cultured on the inhibitory TN-R substrate in vitro. When locally administered into the lesion sites of rats received spinal cord dorsal hemisection, these TN-R antibodies could significantly decrease RhoA activation and improve functional recovery from corticospinal tract (CST) transection. Thus, passive immunotherapy with specific TN-R antagonist may represent a promising repair strategy following acute SCI.

Highlights

► TN-R is an important axonal regeneration inhibitor after SCI. ► We develop TN-R polyclonal antibody which promotes neurite outgrowth in vitro. ► TN-R antibody improves functional recovery in a rat model of SCI. ► Passive immunotherapy with TN-R antagonist is a promising repair strategy after SCI.

Section snippets

Acknowledgments

This research was supported by the Natural Science Foundation of China (NSFC) (U0632008) and Funds for Key Sci-Tech Research Projects of Guangdong Province [YUECAIJIAO (2008) 258-2008A030201019].

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Citation Excerpt :
Accordingly, Tnr is expected to contribute to neurite outgrowth inhibition in the optic nerve [119]. This is in line with the observation that treatment with Tnr-specific antibodies was able to promote functional recovery after spinal cord injury in rats [120]. Studies with KO mice showed differences in the role of Tnc and Tnr after CNS damage.
The tenascin family of glycoproteins comprises four members in vertebrates, of which tenascin-C (Tnc) and tenascin-R (Tnr) are particularly important in the context of lesions in the central nervous system (CNS). Tnc is expressed in the developing CNS, before it is down-regulated and mainly restricted to the adult neural stem cell niches. It regulates numerous processes including differentiation, adhesion, migration and neurite outgrowth. These aspects are critical in the developing organism, but also after damage. Interestingly, Tnc is indeed re-expressed in the injured CNS. Additionally, Tnc is an activator of the immune response, another important aspect after lesion. Tnr is part of perineuronal nets, a specialized form of extracellular matrix that enwraps subtypes of neurons and limits synaptic plasticity. We summarize the role of tenascins in the context of stem cell niches, barrier formation, synaptic plasticity and immune response in the damaged mammalian CNS.
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¹: These authors contributed equally to this work.

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

Abstract

Highlights

Section snippets

Acknowledgments

Neuroscience

Trends in Neurosciences

Experimental Neurology

Molecular and Cellular Neurosciences

Journal of Biological Chemistry

Neuron

Progress in Brain Research

Progress in Neurobiology

Molecular and Cellular Neurosciences

Neuron

Journal of Biological Chemistry

Tenascin-R is antiadhesive for activated microglia that induce downregulation of the protein after peripheral nerve injury: a new role in neuronal protection

Journal of Neuroscience

Tenascin-R restricts posttraumatic remodeling of motoneuron innervation and functional recovery after spinal cord injury in adult mice

Journal of Neuroscience

Expression of janusin (J1-160/180) in the retina and optic nerve of the developing and adult mouse

Glia

A sensitive and reliable locomotor rating scale for open field testing in rats

Journal of Neurotrauma

Tenascin-R as a repellent guidance molecule for developing optic axons in zebrafish

Journal of Neuroscience

Tenascin-R inhibits regrowth of optic fibers in vitro and persists in the optic nerve of mice after injury

Glia