Correlation between GAP43 and nerve growth factor receptors in rat sensory neurons

Verge, Valerie M. K.; Tetzlaff, Wolfram; Richardson, P. M.; Bisby, Mark A.

doi:10.1523/jneurosci.10-03-00926.1990

Cited by 137 publications

(81 citation statements)

References 23 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, NGF and substance P can contribute to nerve ingrowth [1,6,13,44], and without NGF, all sensory neurons will undergo apoptosis [7]. Both factors work in synergy and may be directly involved in mediating innervation and pain in the lower back [35,39]. The current findings and previous reports suggest a possible signaling cascade starting with fibroblast activation, macrophage infiltration, increased vascularization, and ultimately innervation/nociception.…”

Section: Discussionsupporting

confidence: 56%

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Veruva

Lanman

Isaza

et al. 2017

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

Background The pathophysiology and mechanisms driving the generation of unintended pain after total disc replacement (TDR) remain unexplored. Ultrahigh-molecular-weight polyethylene (UHMWPE) wear debris from TDRs is known to induce inflammation, which may result in pain.Questions/purposes The purpose of this study was to determine whether (1) periprosthetic UHMWPE wear debris induces immune responses that lead to the production of tumor necrosis factor-a (TNFa) and interleukin (IL)-1ß, the vascularization factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factorbb (PDGFbb), and the innervation/pain factors, nerve growth factor (NGF) and substance P; (2) the number of Clinical Orthopaedics and Related Research ®A Publication of The Association of Bone and Joint Surgeons® macrophages is associated with the production of the aforementioned factors; (3) the wear debris-induced inflammatory pathogenesis involves an increase in vascularization and associated innervation. Methods Periprosthetic tissues from our collection of 11 patients with contemporary TDRs were evaluated using polarized light microscopy to quantify UHMWPE wear particles. The major reason for revision (mean implantation time of 3 years [range, 1-6 years]) was pain. For control subjects, biopsy samples from four patients with degenerative disc disease with severe pain and autopsy samples from three normal patients with no history of back pain were also investigated. Immunohistochemistry and histology were used to identify secretory factors, macrophages, and blood vessels. Immunostained serial sections were imaged at 9200 magnification and using MATLAB and NIH ImageJ, a threshold was determined for each factor and used to quantify positive staining normalized to tissue sectional area. The Mann-Whitney U test was used to compare results from different patient groups, whereas the Spearman Rho test was used to determine correlations. Significance was based on p \ 0.05. Results The mean percent area of all six inflammatory, vascularization, and innervation factors was higher in TDR tissues when compared with normal disc tissues. Based on nonparametric data analysis, those factors showing the most significant increase included TNFa (5.17 ± 1.76 versus 0.05 ± 0.03, p = 0.02), VEGF (3.02 ± 1.01 versus 0.02 ± 0.002, p = 0.02), and substance P (4.15 ± 1.01 versus 0.08 ± 0.04, p = 0.02). The mean percent area for IL-1ß (2.41 ± 0.66 versus 0.13 ± 0.13, p = 0.01), VEGF (3.02 ± 1.01 versus 0.34 ± 0.29, p = 0.04), and substance P (4.15 ± 1.01 versus 1.05 ± 0.46, p = 0.01) was also higher in TDR tissues when compared with disc tissues from patients with painful degenerative disc disease. Five of the factors, TNFa, IL-1ß, VEGF, NGF, and substance P, strongly correlated with the number of wear particles, macrophages, and blood vessels. The most notable correlations included TNFa with wear particles (p \ 0.001, q = 0.63), VEGF with macrophages (p = 0.001, q = 0.71), and NGF with blood vessels (p\0.001, q = 0.70). Of particular signif...

show abstract

Section: Discussionsupporting

confidence: 56%

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

Veruva

Lanman

Isaza

et al. 2017

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

show abstract

“…One aspect of the cell body response is the upregulation of GAP-43. In uninjured ganglia, a proportion of small to medium-sized cells constitutively express GAP-43 (Verge et al, 1990b;Andersen and Schreyer, 1999), although here we find GAP-43 expression in all sizes of DRG neurons (26% of all profiles; 30% of profiles Ͼ45 m in diameter) (Fig. 2 A).…”

Section: Cell Body Reactionmentioning

confidence: 44%

“…GAP-43 is induced in nearly all neurons during peripheral nerve regeneration (Verge et al, 1990b), but in few neurons after rhizotomy (Schreyer and Skene, 1993), unless the root is severed very close to the DRG (Chong et al, 1996). Dorsal root axonal growth occurs at about half the rate of peripheral axons (Wujek and Lasek, 1983;Oblinger and Lasek, 1984).…”

Section: Abstract: Neurotrophin-3; Regeneration; Degeneration; Astromentioning

confidence: 99%

Two-Tiered Inhibition of Axon Regeneration at the Dorsal Root Entry Zone

Ramer

Duraisingam²,

Priestley

et al. 2001

J. Neurosci.

View full text Add to dashboard Cite

Glial-derived inhibitory molecules and a weak cell-body response prevent sensory axon regeneration into the spinal cord after dorsal root injury. Neurotrophic factors, particularly neurotrophin-3 (NT-3), may increase the regenerative capacity of sensory neurons after dorsal rhizotomy, allowing regeneration across the dorsal root entry zone (DREZ). Intrathecal NT-3, delivered at the time of injury, promoted an upregulation of the growth-associated protein GAP-43 primarily in large-diameter sensory profiles (which did not occur after rhizotomy alone), as well as regeneration of cholera toxin B-labeled sensory axons across the DREZ and deep into the dorsal horn. However, delaying treatment for 1 week compromised regeneration: although axons still penetrated the DREZ, growth within white matter was qualitatively and quantitatively restricted. This was not associated with an impaired cell-body response (GAP-43 upregulation was equivalent for both immediate and delayed treatments), or with astrogliosis at the DREZ, which begins almost immediately after rhizotomy, but with the delayed appearance of mature ED1-expressing phagocytes in the dorsal white matter between 1 and 2 weeks after lesion, marking the beginning of myelin breakdown. After rhizotomy with immediate NT-3 treatment, regeneration continues beyond 2 weeks, but in the dorsal gray matter rather than in the degenerating dorsal columns. The ability of NT-3 to promote regeneration across the DREZ, but not after the beginning of degeneration after delayed treatment reveals a hierarchy of inhibitory influences: the astrogliotic, but not the degenerative barrier is surmountable by NT-3 treatment. Key words: neurotrophin-3; regeneration; degeneration; astrocytes; oligodendrocytes; myelin; dorsal root ganglionThe differential abilities of peripheral and central nervous tissue to support regeneration is exemplified at the dorsal root entry zone (DREZ), which marks the entry point of primary afferent axons into the spinal cord. Here, the environment changes abruptly from consisting of growth-permissive Schwann cells, to astrocytes, oligodendrocytes, and microglia, which may all inhibit regeneration (Fawcett and Asher, 1999). On contact with the DREZ, regenerating axons form club-like end bulbs or synapselike structures, (Ramon y Cajal, 1928;Carlstedt, 1985), but because of the prohibitive environment of the CNS and a paltry regenerative response of sensory neurons to rhizotomy, they never re-enter the adult cord.One strategy to encourage regeneration is to enhance the growth response of the rhizotomized neurons. GAP-43 is induced in nearly all neurons during peripheral nerve regeneration (Verge et al., 1990b), but in few neurons after rhizotomy (Schreyer and Skene, 1993), unless the root is severed very close to the DRG (Chong et al., 1996). Dorsal root axonal growth occurs at about half the rate of peripheral axons (Wujek and Lasek, 1983;Oblinger and Lasek, 1984). An experimental "conditioning" lesion to a peripheral nerve before dorsal rhizotomy doubles the rate of ...

show abstract

“…Similarly, outgrowing axons in the dermis and epidermis express the growth molecule GAP43/B50 at their growth cones, a protein not normally prominent in stable axons (Tetzlaff et al, 1989;Verge et al, 1990;Krekoski et al, 2002). GAP43/B50 serves as an actin-binding protein at the growth cone membrane and its expression is upregulated in both neuronal perikarya and distal outgrowing axons after injury.…”

Section: Discussionmentioning

confidence: 99%