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Doxorubicin (Dox), a topoisomerase interactive agent, is commonly used to treat several types of cancer. This drug is known to cause cognitive impairments in individuals submitted to long-term chemotherapy (deficits also called as chemobrain). The present study investigated whether morphological, oxidative and behavioral impairments could be induced by Dox. Male Wistar rats were injected with Dox (2.5 mg/kg, once every week for 28 days, intraperitoneal route-IP) or 0.9% saline solution (same volume, IP). During the experimental period, behavioral studies were performed, including the open field test, the elevated plus maze, tests for sociability and preference for social novelty and the novel object recognition task. Brains were analyzed by immunohistochemistry (GFAP or glial fibrillary acidic protein expression in astrocytes) and hematoxylin-eosin and luxol fast blue (for myelin) staining techniques, as well as for the assessment of oxidative parameters (thiobarbituric acid reactive substances-TBARS, catalase, superoxide dismutase-SOD, glutathione peroxidase-GPX, glutathione reductase-GR, nitric oxide-NO). Dox-injected rats presented increased GFAP expression in all analyzed areas (frontal cortex, striatum, hippocampus, hypothalamus, granular and molecular layers of the cerebellum). Dox administration also increased the levels of the oxidative indicators TBARS, NO and GR and caused memory impairments as seen in the novel object recognition test. No signs of demyelination and/or neuronal loss were found. Results suggest that astrogliosis and oxidative stress induced by Dox may be linked to chemotherapy-induced memory deficits.

Propentofylline (PPF) is a xanthine derivative that depresses activation of glial cells, whose responses induce oxidative stress and neural tissue damage during inflammation. Ethidium bromide (EB) injection into the brain causes local oligodendroglial and astrocytic loss, resulting in primary demyelination and neuroinflammation. Surviving astrocytes present increased glial fibrillary acidic protein (GFAP) expression around the injury site. This investigation aimed to evaluate the capacity of PPF of affecting glial cell behaviour during the process of demyelination-remyelination and of altering cytokine release and lipid peroxidation (measured through its byproducts TBARS or thiobarbituric acid reactive species) in the plasma and brain. Wistar rats were injected with 0.1%EB into the cisterna pontis and treated or not with PPF (12.5 mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from day (D) 7 to 31 and processed for GFAP immunohistochemistry and ultrastructural investigation. A semi-quantitative method was used to compare remyelination status. Plasma and brains were also collected for TBARS and cytokines (IL-1beta and TNF-alpha, measured by ELISA). PPF treatment decreased the levels of TBARS and cytokines in plasma and brains of EB-injected rats until D15, reduced GFAP expression until D21, and increased both oligodendroglial and Schwann cell remyelination on D31. These data suggest that PPF stimulates remyelination, decreases inflammation and redox imbalances in plasma and brain and may have a preventive role in glial scar development following gliotoxic injury.