TEMPORAL DYNAMICS OF ULTRASTRUCTURAL DAMAGE TO THE RAT SCIATIC NERVE UNDER THE EFFECTS OF CISPLATIN, PACLITAXEL, AND THEIR CONCURRENT ADMINISTRATION

Authors:

Abstract:

Chemotherapy-induced peripheral neuropathy remains one of the most common dose-limiting complications of cisplatin- and paclitaxel-based regimens. The aim of the study was to characterize the ultrastructural changes and their temporal dynamics in the rat sciatic nerve following separate and combined administration of these agents. Adult male inbred rats were divided into four groups: intact control, paclitaxel (cumulative dose 8 mg/kg i.p.), cisplatin (cumulative dose 16 mg/kg i.p.), and a combination group. During concurrent administration, animals received cisplatin at a dose of 2 mg/kg and paclitaxel at a dose of 5 mg/kg once weekly for six weeks. The selected regimen provided a cumulative dose exposure comparable to standard clinical protocols of paclitaxel (175 mg/m²) and cisplatin (75 mg/m²) when converted on the basis of body surface area. Sciatic nerve specimens were examined by transmission electron microscopy on days 1, 7, 60, 90, and 120 after treatment initiation, with morphometric assessment of endoneurial capillary basal lamina thickness. Cisplatin induced early and pronounced endothelial-vascular damage (basal lamina thickening up to 255±30 nm, increased micropinocytosis, blood stasis, and perivascular oedema). Paclitaxel predominantly affected the axon-glial unit, causing periaxonal vacuolization, early myelin splitting, and mitochondrial degeneration in Schwann cells. Concurrent administration produced synergistic destruction of all neuro-glio-vascular components, with the most severe basal lamina thickening (280±33 nm at day 90), total myelin disorganization, massive axonal loss, and endoneurial fibrosis. By day 120, only partial recovery was observed, with persistent basal lamina thickening and chronic axonal atrophy. The results demonstrate that endothelial dysfunction and impairment of the blood-nerve barrier represent the earliest and leading events in the CIPN cascade. These findings provide morphological evidence for the development of early neuroprotective strategies focused on stabilization of the blood-nerve barrier and mitochondrial homeostasis in patients receiving cisplatin- and paclitaxel-containing chemotherapy.

Keywords:

chemotherapy-induced peripheral neuropathy cisplatin paclitaxel sciatic nerve ultrastructure blood-nerve barrier transmission electron microscopy

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Publication:

«World of Medicine and Biology» Vol. 22 No. 1 (2026) , с. 190-198
УДК 616.833-009.17-092.9:615.277

DOI:

https://doi.org/10.26724/2079-8334-2026-1-95-190-198