Abstract
<jats:p>Paclitaxel is a widely used taxane antineoplastic agent, and its administration is frequently associated with neurotoxic complications affecting both the peripheral and central nervous systems. While chemotherapy-induced peripheral neuropathy has been extensively characterized, central morphological alterations particularly in the cerebellum remain insufficiently investigated. The cerebellum is a functionally critical structure involved in motor coordination and sensorimotor integration; it is especially vulnerable to toxic injury due to the high metabolic demands of its neurons (primarily Purkinje cells) and the structural and functional dependence on intact neurogliovascular units. The aim of this study was to evaluate morphological and morphometric changes in the rat cerebellum following paclitaxel-induced neurotoxicity and to assess the corrective potential of therapeutic vortioxetine administration. The study was conducted on adult male white rats. Neurotoxicity was induced by intraperitoneal administration of paclitaxel at a dose of 2 mg/kg (four injections every other day), resulting in a cumulative dose of 8 mg/kg. Therapeutic correction was performed via intragastric vortioxetine at a dose of 5 mg/kg once daily for 14 days, starting immediately after completion of paclitaxel treatment. Cerebellar morphology was examined on days 14, 28, 60, 90, and 120 using light microscopy after hematoxylin and eosin staining, followed by digital morphometric analysis of cortical layer thickness and Purkinje cell parameters. Motor function was assessed through behavioral tests evaluating locomotor activity and coordination. Paclitaxel exposure led to time-dependent structural alterations in the cerebellar cortex. Early changes included moderate neuropil edema and focal chromatin condensation in Purkinje cells. At the peak of toxic load (day 28), partial disorganization of the Purkinje cell layer, reduced cortical thickness, and focal neuropil homogenization were observed. Morphometric analysis revealed significant reductions in the thickness of the molecular, Purkinje, and granular layers, decreased Purkinje cell density, and reduced soma and nuclear areas. At later time points, gradual spontaneous recovery occurred but remained incomplete in untreated animals. Therapeutic vortioxetine administration attenuated the severity of cerebellar damage, limited disorganization of the Purkinje cell layer, and promoted preservation of neuronal morphology. From days 60 to 120, reparative changes predominated, with partial restoration of laminar organization and normalization of morphometric indices toward control values. Behavioral assessments demonstrated persistent motor impairment following paclitaxel administration, whereas vortioxetine contributed to partial functional compensation, as evidenced by improved locomotor activity and motor coordination. These findings indicate that therapeutic vortioxetine administration mitigates paclitaxel-induced cerebellar structural damage and supports reparative processes, highlighting its potential role in the post-toxic correction of central nervous system involvement.</jats:p>