Nonsteroidal Anti-Inflammatory Drugs Promote Axon Regeneration via RhoA Inhibition

Fu, Qiao; Hue, Jeongsim; Li, Shuxin

doi:10.1523/jneurosci.4353-06.2007

Cited by 162 publications

(218 citation statements)

References 62 publications

(95 reference statements)

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“…Unlike most other nonsteroidal anti-inflammatory drugs, ibuprofen suppresses basal RhoA activity (Zhou et al, 2003). A recent report suggested that ibuprofen promotes corticospinal axon regeneration after spinal cord injury (Fu et al, 2007). Here, we confirm that ibuprofen reduces ligand-induced Rho signaling and myelin-induced inhibition of neurite outgrowth in vitro.…”

supporting

confidence: 81%

“…This may relate to acute versus chronic activities, to different inhibitor presentations, or to different cell types Mehta et al, 2007;Venkatesh et al, 2007). The in-vitro data reveal a less complete abolition of Rho signaling than that seen in previous studies (Fu et al, 2007), but they suggest that ibuprofen might promote injury-induced growth of CNS axons in vivo.…”

Section: Fig 1 Ibuprofen Inhibits Ligand-induced Rho Activation Andmentioning

confidence: 62%

“…Published work has shown that ibuprofen and a selected subset of NSAIDs can inhibit basal Rho activity via a mechanism independent from cyclooxygenase inhibition (Fu et al, 2007;Jin et al, 2006;Zhou et al, 2003). We examined whether ibuprofen prevents receptor-activated Rho activity, in addition to basal activity.…”

Section: Ibuprofen Blocks Rho-mediated Signalingmentioning

confidence: 99%

“…One study demonstrated that ibuprofen and several other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce RhoA activation (Zhou et al, 2003). Recently, it was reported that ibuprofen prevents myelin inhibition of outgrowth by reducing Rho activation, and also stimulates corticospinal axonal regeneration after spinal cord injury (Fu et al, 2007).…”

mentioning

confidence: 99%

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Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth

Wang

Budel

Baughman

et al. 2009

Journal of Neurotrauma

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The GTP-binding protein RhoA regulates microfilament dynamics in many cell types and mediates the inhibition of axonal regeneration by myelin and chondroitin sulfate proteoglycans. Unlike most other nonsteroidal anti-inflammatory drugs, ibuprofen suppresses basal RhoA activity (Zhou et al., 2003). A recent report suggested that ibuprofen promotes corticospinal axon regeneration after spinal cord injury (Fu et al., 2007). Here, we confirm that ibuprofen reduces ligand-induced Rho signaling and myelin-induced inhibition of neurite outgrowth in vitro. Following 4 weeks of subcutaneous administration of ibuprofen, beginning 3 days after spinal cord contusion, animals recovered walking function to a greater degree, with twice as many rats achieving a hind limb weight-bearing status. We examined the relative role of tissue sparing, axonal sprouting, and axonal regeneration in the action of ibuprofen. Histologically, ibuprofen-treated animals display an increase in spared tissue without an alteration in astrocytic or microglial reaction. Ibuprofen increases axonal sprouting from serotonergic raphespinal axons, and from rostral corticospinal fibers in the injured spinal cord, but does not permit caudal corticospinal regeneration after spinal contusion. Treatment of mice with complete spinal cord transection demonstrates long-distance raphespinal axon regeneration in the presence of ibuprofen. Thus, administration of ibuprofen improves the recovery of rats from a clinically relevant spinal cord trauma by protecting tissue, stimulating axonal sprouting, and allowing a minor degree of raphespinal regeneration.

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supporting

confidence: 81%

Section: Fig 1 Ibuprofen Inhibits Ligand-induced Rho Activation Andmentioning

confidence: 62%

Section: Ibuprofen Blocks Rho-mediated Signalingmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth

Wang

Budel

Baughman

et al. 2009

Journal of Neurotrauma

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“…Multiple additional mechanisms of neuroprotection for NSAIDs have been proposed. These include inhibition of ␥-secretase activity, A␤ secretion, and A␤ aggregation (especially by ibuprofen (22)) as well as stimulation of neurite outgrowth by some NSAIDs (ibuprofen and indomethacin), but not by naproxen (14,23). It is unclear which of these mechanisms reflect the activity of COX enzymes as opposed to other targets of particular structural classes of NSAIDs (24).…”

Section: Discussionmentioning

confidence: 99%

Identification of Small Molecule Inhibitors of Neurite Loss Induced by Aβ peptide using High Content Screening

Ofengeim

Shi

Miao

et al. 2012

Journal of Biological Chemistry

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Background: Amyloid-␤-induced degeneration of neurites is a key event in Alzheimer disease. Results: We describe NeuriteIQ high content screening platform for analysis of neurite degeneration. Conclusion: We identified multiple cyclooxygenase inhibitors and agonists of PPAR␥ as suppressors of A␤-induced neurite loss. Significance: Our study demonstrates the feasibility of using NeuriteQ to discover inhibitors of neurite loss and provide a new insight into neurite degeneration.

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Cell and Tissue Instructive Materials for Central Nervous System Repair

Rocha

Silva

Barata‐Antunes

et al. 2020

Adv Funct Materials

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Neurodegenerative disorders and traumatic events affecting the central nervous system (CNS) represent one of the main health problems nowadays. The level of disability and impairment of these patients is very high, both at physiological and psychological level, drastically altering a person's lifestyle. The fact that CNS tissue has a limited capacity of regeneration has hampered the development of possible therapies to these conditions. The specificity of each disease also increases the complexity of creating strategies capable of inducing significant recovery. Therefore, the search for a solution for these problems most likely demands a combinatorial approach that integrates knowledge from different fields. Tissue engineering and regenerative medicine (TERM) concepts merge areas such as biology, chemistry, physics, or biomaterials science, and it is a strong candidate for CNS applications. In particular, the development of cell and tissue instructive materials (CTIMs) can bring new opportunities for the treatment of these conditions. In this review, the authors summarize and discuss the most recent advances in the development of CTIMs for CNS applications, focusing on traumatic conditions such as spinal cord injuy, traumatic brain injuy, but also stroke, and other neurodegenerative diseases such as Alzheimer's and Parkinson's disease as well as multiple sclerosis.

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Nonsteroidal Anti-Inflammatory Drugs Promote Axon Regeneration via RhoA Inhibition

Cited by 162 publications

References 62 publications

Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth

Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth

Identification of Small Molecule Inhibitors of Neurite Loss Induced by Aβ peptide using High Content Screening

Cell and Tissue Instructive Materials for Central Nervous System Repair

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