Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats

Persohn, Elke; Canta, A; Schoepfer, S.; Traebert, Martin; Mueller, Lutz Peter; Gilardini, Alessandra; Galbiati, Sara; Nicolini, Gabriella; Scuteri, A; Lanzani, Francesca; Giussani, Giuditta; Cavaletti, Guido

doi:10.1016/j.ejca.2005.04.006

Cited by 117 publications

(67 citation statements)

References 23 publications

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“…Interestingly, the Schwann cells showing ATF-3 up-regulation tended to be arranged in a linear fashion as if a group of Schwann cells that ensheath the same injured axon were all expressing ATF3. These data are consistent with previous morphological and ultrastructural studies which showed pronounced degenerative changes in Schwann cells and axons located within the sciatic nerve and dorsal roots, but not ventral roots of rats that received intravenous infusion of paclitaxel (Cliffer et al, 1998;Persohn et al, 2005).…”

Section: Cellular Alterations In Satellite Cells Macrophages and Schsupporting

confidence: 93%

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

et al. 2007

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Paclitaxel (Taxol®) is a frontline antineoplastic agent used to treat a variety of solid tumors including breast, ovarian, or lung cancer. The major dose limiting side effect of paclitaxel is a peripheral sensory neuropathy that can last days to a lifetime. To begin to understand the cellular events that contribute to this neuropathy, we examined a marker of cell injury/regeneration (activating transcription factor 3; ATF3), macrophage hyperplasia/hypertrophy; satellite cell hypertrophy in the dorsal root ganglion (DRG) and sciatic nerve as well as astrocyte and microglial activation within the spinal cord at 1, 4, 6 and 10 days following intravenous infusion of therapeutically relevant doses of paclitaxel. At day 1 post-infusion there was an up-regulation of ATF3 in a subpopulation of large and small DRG neurons and this up-regulation was present through day 10. In contrast, hypertrophy of DRG satellite cells, hypertrophy and hyperplasia of CD68+ macrophages in the DRG and sciatic nerve, ATF3 expression in S100β+ Schwann cells and increased expression of the microglial marker (CD11b) and the astrocyte marker glial fibrillary acidic protein in the spinal cord were not observed until day 6 post infusion. The present results demonstrate that using the time points and markers examined, DRG neurons show the first sign of injury which is followed days later by other neuropathological changes in the DRG, peripheral nerve and dorsal horn of the spinal cord. Understanding the cellular changes that generate and maintain this neuropathy may allow the development of mechanism-based therapies to attenuate or block this frequently painful and debilitating condition.

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Section: Cellular Alterations In Satellite Cells Macrophages and Schsupporting

confidence: 93%

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

et al. 2007

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“…Our results showed that sciatic nerve had degenerative changes in the form of axonopathy (irregular compressed axoplasm, swollen mitochondria and myelin figures) and myleinopathy (irregular thickening, disruption and splitting). These findings coincide with previous reports whereas sciatic nerve of paclitaxel-treated animals showed axonopathy including collapse and fragmentation of the myelin sheath of some axons [32] .…”

Section: Discussionsupporting

confidence: 82%

The Possible Role of Propolis in Ameliorating Paclitaxel-Induced Peripheral Neuropathy in Sciatic Nerve of Adult Male Albino Rats

Kassab

Elkaliny

2017

Egyptian Journal of Histology

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Background: Paclitaxel is a neurotoxic chemotherapeutic agent. The sensorimotor peripheral neuropathy is a serious dose limiting complication of paclitaxel therapy. Propolis is a natural honeybee product collected from plants. It has broad biological and pharmacological activities and a proposed neuroprotective role. Aim: To assess the possible protective role of propolis on paclitaxel-induced peripheral neuropathy in rat's sciatic nerve. Material and Methods: Twenty-four adult male albino rats were divided into four equal groups; control group, propolistreated group (50 mg/kg orally once daily), paclitaxel -treated group (16 mg/kg intraperitoneally once a week), and both paclitaxel & propolis-treated group. Animals were treated for 5 consecutive weeks. Specimens of sciatic nerve were processed for histological study by light and electron microscopy. Immunohistochemical study was carried out using CD68 antibody. Morphometric study and statistical analysis of light microscopic data were performed for all groups. Results: Compared to the control group, the sciatic nerve specimens of the paclitaxel-treated rats showed splitting of myelin lamellae with infolded myelin loops, together with invagination and evagination of the myelin sheath. Changes in the axons included formation of myelin figures, compression and irregularity. Schwann cells showed cytoplasmic vacuolation and dilated rER. Immunohistochemical study revealed a significant increase in the number of CD68 positive cells. On the other hand, minimal changes were observed in rats treated concomitantly with both paclitaxel and propolis, with a non-significant increase in CD68 positive cells. Conclusion: Paclitaxel induced structural changes in the myelinated fibers of sciatic nerve of albino rats. The concomitant treatment with propolis ameliorated these changes.

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“…In this study, paclitaxel treatment caused mechanical allodynia/hyperalgesia and a reduction of SNCV, as previously described (Polomano et al, 2001;Persohn et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

et al. 2011

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Paclitaxel is one of the most commonly used anti-neoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involvement of L-serine in paclitaxel-induced hyperalgesia/allodynia and decrease in sensory nerve conduction velocity (SNCV). We used a preclinical rat model of paclitaxel-induced painful

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Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats

Cited by 117 publications

References 23 publications

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

The Possible Role of Propolis in Ameliorating Paclitaxel-Induced Peripheral Neuropathy in Sciatic Nerve of Adult Male Albino Rats

Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

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