Reduction in CNS scar formation without concomitant increase in axon regeneration following treatment of adult rat brain with a combination of antibodies to TGFβ1 and β2

  title={Reduction in CNS scar formation without concomitant increase in axon regeneration following treatment of adult rat brain with a combination of antibodies to TGF$\beta$1 and $\beta$2},
  author={Lawrence David Falcon Moon and James W. Fawcett},
  journal={European Journal of Neuroscience},
  • L. Moon, J. Fawcett
  • Published 1 November 2001
  • Biology, Medicine
  • European Journal of Neuroscience
In this study we investigated whether CNS axons regenerate following attenuation of scar formation using a combination of antibodies against two isoforms of transforming growth factor beta (TGFβ). Anaesthetized adult rats were given unilateral mechanical lesions of the nigrostriatal tract. Implantation of transcranial cannulae allowed wounds to be treated with a combination of antibodies against TGFβ1 and TGFβ2 once daily for 10 days postaxotomy. Eleven days post‐transection brains from animals… 

Pharmacological Suppression of CNS Scarring by Deferoxamine Reduces Lesion Volume and Increases Regeneration in an In Vitro Model for Astroglial-Fibrotic Scarring and in Rat Spinal Cord Injury In Vivo

The in vitro model for CNS scarring is suitable for efficient pre-screening and identification of putative scar-suppressing agents prior to in vivo application and validation, thus saving costs, time and laboratory animals.

Small molecule inhibitor of type I transforming growth factor‐β receptor kinase ameliorates the inhibitory milieu in injured brain and promotes regeneration of nigrostriatal dopaminergic axons

Results indicate that inhibition of TGF‐β signaling suppresses formation of the fibrotic scar and creates a permissive environment for axonal regeneration.

NG2 proteoglycan‐expressing cells of the adult rat brain: Possible involvement in the formation of glial scar astrocytes following stab wound

The combined detection of glial markers within cells present in the lesioned area indicated that, although they rarely express GFAP, the marker of mature astrocytes, NG2+ cells located along the lesion borders frequently express nestin and vimentin, i.e., two markers of immature astroCytes.

Expression of Transforming Growth Factor-β Receptors in Meningeal Fibroblasts of the Injured Mouse Brain

Results indicate that meningeal fibroblasts not reactive astrocytes are a major target of TGF-β1 that is upregulated after CNS injury.

VU Research Portal Inhibitors of spinal cord regeneration

It is concluded that neuron-specific targeting of a single ligand-receptor pair (Sema3A/Npn-1) in the multi-component, divergent semaphorin/neuropilin/ plexin signalling pathway is insufficient to enhance regeneration of the CST.

TGF-β1 and TGF-β2 expression after traumatic human spinal cord injury

The early induction of TGF-β1 at the point of SCI suggests a role in the acute inflammatory response and formation of the glial scar, while the later induction ofTGF- β2 may indicate a roles in the maintenance of the scar.

Intracellular mediators of axonal sprouting in vivo

Overall, data from facial nucleus studies suggest central axonal sprouting is an injury but not a reinnervation-driven response that it is not directly connected to neuronal cell death, that excessive inflammation is detrimental, and that jun-, Ras-, and MEK1-mediated changes in regeneration-associated gene and protein expression play a vital part in shaping the growth cone response.

Inhibition of TGF-β1 promotes functional recovery after spinal cord injury




Effects of Transforming Growth Factor β1, on Scar Production in the Injured Central Nervous System of the Rat

It is demonstrated that transforming growth factor β1 participates in the scarring response in the rat brain, and the potential use for TGFβ1 antagonists as inhibitors of scar formation in the injured mammalian CNS is self‐evident.

Robust Regeneration of CNS Axons through a Track Depleted of CNS Glia

The results suggest that control of the glial reaction is likely to be an important feature in brain repair and that reports of axon regeneration must be interpreted with caution since extensive regeneration can occur simply as a result of a major glia-depleting lesion, rather than as the result of some other specific intervention.

Antibody to Transforming Growth Factor Beta Reduces Collagen Production in Injured Peripheral Nerve

A significant reduction in total pixel count and in total number of fibroblasts per high‐power field was found in crushed rat sciatic nerve treated with anti‐TGF‐&bgr; antibody when compared with those treated only with phosphate‐buffered saline.

Cytokine‐induced changes in the ability of astrocytes to support migration of oligodendrocyte precursors and axon growth

This work examined neuritic outgrowth from dorsal root ganglion explants in three‐dimensional astrocyte cultures treated with cytokines and found that IL‐1α + bFGF greatly increased axon outgrowth and that this effect could be blocked by TGFβ and IFNγ.

Decorin Attenuates Gliotic Scar Formation in the Rat Cerebral Hemisphere

The findings suggest that decorin is potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components and maintain and/or restore functional integrity.

Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor‐β2

The findings suggest that such synthetic anti‐fibrotic TGF‐β antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.

Neurocan Is Upregulated in Injured Brain and in Cytokine-Treated Astrocytes

It is shown that the CSPG neurocan, which is expressed in the CNS, exerts a repulsive effect on growing cerebellar axons and raises the possibility that neurocan interferes with axonal regeneration after CNS injury.

Macrophage/Microglia Regulation of Astrocytic Tenascin: Synergistic Action of Transforming Growth Factor-β and Basic Fibroblast Growth Factor

Results show that the regulation of astrocytic tenascin is mediated by the synergistic action of TGF-β1 and bFGF in vitro and after injury in vivo.

Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC

It is demonstrated that it is possible to enhance CNS axon regeneration in the adult rat nigrostriatal tract following chondroitinase ABC degradation of chondDetroitin sulfate.