Antiallodynic action of phosphodiesterase inhibitors in a mouse model of peripheral nerve injury

Megat, Salim; Hugel, Sylvain; Journée, Sarah H.; Bohren, Yohann; Lacaud, Adrien; Lelièvre, Vincent; Doridot, Stéphane; Villa, Pascal; Bourguignon, Jean‐Jacques; Salvat, Éric; Schlichter, Rémy; Freund-Mercier, Marie José; Yalçın, İpek; Barrot, Michel

doi:10.1016/j.neuropharm.2021.108909

Cited by 4 publications

(2 citation statements)

References 86 publications

(99 reference statements)

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“…[74] Additionally, it has neuroprotective properties and may exert antiallodynic effects. [75,76] These findings are crucial for the treatment of lower limb neurological symptoms of LSS. In summary, the antifibrotic and antiallodynic effects of rolipram make it a promising treatment option for LSS.…”

Section: Potential Therapeutic Strategies Of Lssmentioning

confidence: 99%

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review

Fang,

Wang,

Jiang

et al. 2024

Medicine

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Lumbar spinal stenosis (LSS) can cause a range of cauda equina symptoms, including lower back and leg pain, numbness, and intermittent claudication. This disease affects approximately 103 million people worldwide, particularly the elderly, and can seriously compromise their health and well-being. Ligamentum flavum hypertrophy (LFH) is one of the main contributing factors to this disease. Surgical treatment is currently recommended for LSS caused by LFH. For patients who do not meet the criteria for surgery, symptom relief can be achieved by using oral nonsteroidal anti-inflammatory drugs (NSAIDs) and epidural steroid injections. Exercise therapy and needle knife can also help to reduce the effects of mechanical stress. However, the effectiveness of these methods varies, and targeting the delay in LF hypertrophy is challenging. Therefore, further research and development of new drugs is necessary to address this issue. Several new drugs, including cyclopamine and N-acetyl-l-cysteine, are currently undergoing testing and may serve as new treatments for LSS caused by LFH.

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Section: Potential Therapeutic Strategies Of Lssmentioning

confidence: 99%

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review

Fang,

Wang,

Jiang

et al. 2024

Medicine

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“…Increasing evidence suggest that PDEs are implicated in the pathophysiology of many neuronal diseases (Angelopoulou, Pyrgelis, & Piperi, 2022). Pharmacological screening of several PDE inhibitors showed that PDE4 and PDE5 inhibition significantly relieved mechanical hypersensitivity in a mouse model of peripheral nerve injury (Megat et al, 2022). Additionally, both MIF and PDE4 are involved in neuroinflammatory processes through the regulation of inflammatory responses in microglia (Hertz et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Ibudilast Protects Retinal Bipolar Cells from Excitotoxic Retinal Damage and Activates the mTOR Pathway

Hamadmad,

Heisler-Taylor,

Goswami

et al. 2024

Preprint

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Ibudilast, an inhibitor of macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE), has been recently shown to have neuroprotective effects in a variety of neurologic diseases. We utilize a chick excitotoxic retinal damage model to investigate ibudilast's potential to protect retinal neurons. Using single cell RNA-sequencing (scRNA-seq), we find that MIF, putative MIF receptors CD74 and CD44, and several PDEs are upregulated in different retinal cells during damage. Intravitreal ibudilast is well tolerated in the eye and causes no evidence of toxicity. Ibudilast effectively protects neurons in the inner nuclear layer from NMDA-induced cell death, restores retinal layer thickness on spectral domain optical coherence tomography, and preserves retinal neuron function, particularly for the ON bipolar cells, as assessed by electroretinography. PDE inhibition seems essential for ibudilast's neuroprotection, as AV1013, the analogue that lacks PDE inhibitor activity, is ineffective. scRNA-seq analysis reveals upregulation of multiple signaling pathways, including mTOR, in damaged Müller glia (MG) with ibudilast treatment compared to AV1013. Components of mTORC1 and mTORC2 are upregulated in both bipolar cells and MG with ibudilast. The mTOR inhibitor rapamycin blocked accumulation of pS6 but did not reduce TUNEL positive dying cells. Additionally, through ligand-receptor interaction analysis, crosstalk between bipolar cells and MG may be important for neuroprotection. We have identified several paracrine signaling pathways that are known to contribute to cell survival and neuroprotection and might play essential roles in ibudilast function. These findings highlight ibudilast's potential to protect inner retinal neurons during damage and show promise for future clinical translation.

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Endogenous opiates and behavior: 2022

Bodnar

2023

Peptides

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Antiallodynic action of phosphodiesterase inhibitors in a mouse model of peripheral nerve injury

Cited by 4 publications

References 86 publications

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review

Ibudilast Protects Retinal Bipolar Cells from Excitotoxic Retinal Damage and Activates the mTOR Pathway

Endogenous opiates and behavior: 2022

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