Neurotrophins Reduce Degeneration of Injured Ascending Sensory and Corticospinal Motor Axons in Adult Rat Spinal Cord

Sayer, Faisal T.; Oudega, Martin; Hagg, Theo

doi:10.1006/exnr.2002.7901

Cited by 79 publications

(41 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BDNF may also be involved in the suppression of injury-induced delayed apoptosis [50], possibly through the increase of the antiapoptotic molecule, Bcl-xl [51]. An alternative mechanism for the neuroprotective effect of BDNF could be a BDNFregulated reduction of the number of terminal clubs formed at the distal axonal stumps in the rostral cord [52]. Terminal clubs are formed by continuous anterograde axonal transport after transection and sealing of the axon [53] and contain hydrolytic enzymes that contribute to nervous tissue loss [1,2,54].…”

Section: Discussionmentioning

confidence: 99%

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

et al. 2004

Self Cite

View full text Add to dashboard Cite

The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use of poly(D,L-lactic acid) foams, with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response.

show abstract

Section: Discussionmentioning

confidence: 99%

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…These include increased choline acetyl transferase in motoneurons (Yan et al, 1994), increased expression of GAP-43 (Kobayashi et al, 1997) and increased myelin-basic protein (Ikeda et al, 2002). Neurotrophic factors and their receptors are present in developing and in adult spinal cord neurons (Buck et al, 2000;Dreyfus et al, 1999;Schober et al, 1999) suggesting they may play a role in development and in neuronal survival and axonal regeneration (Sayer et al, 2002;Thoenen, 1995). Progesterone receptors, like neurotrophin receptors, are also found on motoneurons (Labombarda et al, 2000).…”

Section: Spinal Cordmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

186

117

View full text Add to dashboard Cite

Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

show abstract

“…Therefore, signaling between neuronderived NRG and Schwann cell-produced neurotrophic factors may have an important role in repairing peripheral nerves after injury. Consistently, both NRGs and neurotrophic factors have been tried therapeutically in humans and in animal models of PNS and CNS diseases that include amyotrophic lateral sclerosis, multiple sclerosis, epileptic seizures, Alzheimer's disease, Parkinson's disease, and traumatic spinal cord injuries (Seeburger and Springer, 1993;Unsicker, 1994;McMahon and Priestley, 1995;Marchionni et al, 1996;Cannella et al, 1998;Apfel, 1999;ter Laak et al, 2000;Coumans et al, 2001;Viehover et al, 2001;Massa et al, 2002;Sayer et al, 2002). Understanding the dynamics of NRG-neurotrophic factor signaling at the axoglial and neuromuscular interfaces will be important for the rational development of new treatments for these conditions, and this study is the first demonstration of a direct soluble growth factor-mediated axoglial communication system involving axonal NRG and Schwann cell neurotrophic factors.…”

Section: Rapid Axoglial Communication Through Schwann Cell Neurotrophmentioning

confidence: 99%

Rapid Axoglial Signaling Mediated by Neuregulin and Neurotrophic Factors

Esper¹,

Loeb²

2004

J. Neurosci.

View full text Add to dashboard Cite

During peripheral nervous system development, Schwann cells are precisely matched to the axons that they support. This is mediated by axonal neuregulins that are essential for Schwann cell survival and differentiation. Here, we show that sensory and motor axons rapidly release heparin-binding forms of neuregulin in response to Schwann cell-derived neurotrophic factors in a dose-dependent manner. Neuregulin release occurs within minutes, is saturable, and occurs from axons that were isolated using a newly designed chamber slide apparatus. Although NGF and glial cell line-derived neurotrophic factor (GDNF) were the most potent neurotrophic factors to release neuregulin from sensory neurons, GDNF and BDNF were most potent for motor neurons and were the predominant neuregulin-releasing neurotrophic factors produced by cultured Schwann cells. Comparable levels of neuregulin could be released at a similar rate from neurons after protein kinase C activation with the phorbol ester, phorbol 12-myristate 13-acetate, which has also been shown to promote the cleavage and release of neuregulin from its transmembrane precursor. The rapid release of neuregulin from axons in response to Schwann cell-derived neurotrophic factors may be part of a spatially restricted system of communication at the axoglial interface important for proper peripheral nerve development, function, and repair.

show abstract

Neurotrophins Reduce Degeneration of Injured Ascending Sensory and Corticospinal Motor Axons in Adult Rat Spinal Cord

Cited by 79 publications

References 105 publications

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

Neurosteroid regulation of central nervous system development

Rapid Axoglial Signaling Mediated by Neuregulin and Neurotrophic Factors

Contact Info

Product

Resources

About