Neurophysiological and neuropathological characterization of new murine models of chemotherapy-induced chronic peripheral neuropathies

Carozzi, Valentina Alda; Canta, A; Oggioni, N; Sala, Barbara; Chiorazzi, A; Meregalli, C; Bossi, M; Marmiroli, P; Cavaletti, Guido

doi:10.1016/j.expneurol.2010.09.004

Cited by 97 publications

(98 citation statements)

References 46 publications

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“…18,26 Most of these results, included the involvement of DRG, were independently confirmed in similar studies in mice. 19,20 In this model we assessed for the first time the temporal profile of proteasome inhibition within PBMC and nervous tissue following BTZ administration. As expected, after the acute delivery, maximal proteasome inhibition (i.e., more than 80%) was present in PBMC, with a progressive reduction of the inhibition (however still present) during the subsequent 48 h. 27,28 Remarkably, a similar extent of inhibition and time course was observed in the sciatic nerve.…”

Section: Discussionmentioning

confidence: 99%

“…37,38 We aimed at achieving proteasomal inhibition in a range close to that observed in our rat model. Based on the available results regarding BTZ neurotoxicity and cellular models of chemotherapy-induced peripheral neurotoxicity, 18,19,39 we selected DRG neurons for the in vitro studies and to rule out possible effects due to incomplete maturation of the proteasomal activity; we tested in parallel the most commonly used E15 and adult neuronal cultures.…”

Section: Discussionmentioning

confidence: 99%

“…18,19,43 Briefly, tissues were removed and fixed for 3 h at room temperature in 3% glutaraldehyde, post-fixed in OsO 4 , and resin embedded. Morphological analysis was performed on 1-µm semi-thin sections stained with toluidine blue.…”

Section: Histopathological Analysis On Drg Sciatic and Caudal Nervesmentioning

confidence: 99%

“…16,17 Pathogenic hypotheses can be reliably investigated in vivo using well-characterized animal models reproducing chronic BiPN as well as neuronal systems in vitro. [18][19][20][21] In this context, we have studied for the first time, using parallel in vivo and in vitro experiments, the possible correlation existing between proteasome inhibition and α-tubulin polymerization in order to understand the pathogenic basis of BiPN onset.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Histopathological Analysis On Drg Sciatic and Caudal Nervesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy

et al. 2013

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“…Previous studies have described rat and mouse models of peripheral neuropathy induced by repeated and prolonged administration of bortezomib (25)(26)(27)(28). On the basis of these findings, in the first series of experiments, we explored whether a single administration of bortezomib produced mechanical and cold hypersensitivity in mice, as observed for different chemotherapeutic agents including oxaliplatin, paclitaxel, and vincristine (4,6,29).…”

Section: Chemotherapy-induced Painful Neuropathy Modelsmentioning

confidence: 99%

Novel Therapeutic Strategy to Prevent Chemotherapy-Induced Persistent Sensory Neuropathy By TRPA1 Blockade

et al. 2013

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Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and painful adverse reaction of cancer treatment in patients that is little understood or treated. Cytotoxic drugs that cause CIPN exert their effects by increasing oxidative stress, which activates the ion channel TRPA1 expressed by nociceptors. In this study, we evaluated whether TRPA1 acted as a critical mediator of CIPN by bortezomib or oxaliplatin in a mouse model system. Bortezomib evoked a prolonged mechanical, cold, and selective chemical hypersensitivity (the latter against the TRPA1 agonist allyl isothiocyanate). This CIPN hypersensitivity phenotype that was stably established by bortezomib could be transiently reverted by systemic or local treatment with the TRPA1 antagonist HC-030031. A similar effect was produced by the oxidative stress scavenger a-lipoic acid. Notably, the CIPN phenotype was abolished completely in mice that were genetically deficient in TRPA1, highlighting its essential role. Administration of bortezomib or oxaliplatin, which also elicits TRPA1-dependent hypersensitivity, produced a rapid, transient increase in plasma of carboxy-methyl-lysine, a by-product of oxidative stress. Short-term systemic treatment with either HC-030031 or a-lipoic acid could completely prevent hypersensitivity if administered before the cytotoxic drug. Our findings highlight a key role for early activation/sensitization of TRPA1 by oxidative stress byproducts in producing CIPN. Furthermore, they suggest prevention strategies for CIPN in patients through the use of early, short-term treatments with TRPA1 antagonists. Cancer Res; 73(10); 3120-31. Ó2013 AACR.

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Interventions for preventing neuropathy caused by cisplatin and related compounds

Albers

Chaudhry²,

Cavaletti

et al. 2011

Cochrane Database of Systematic Reviews

140

139

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Background-Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.Objectives-To examine the efficacy of purported chemoprotective agents to prevent or limit the neurotoxicity of cisplatin and related agents.

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Neurophysiological and neuropathological characterization of new murine models of chemotherapy-induced chronic peripheral neuropathies

Cited by 97 publications

References 46 publications

Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy

Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy

Novel Therapeutic Strategy to Prevent Chemotherapy-Induced Persistent Sensory Neuropathy By TRPA1 Blockade

Interventions for preventing neuropathy caused by cisplatin and related compounds

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