Cisplatin-induced toxicity in the hippocampus: a dose-dependent mechanism of damage

Cisplatin, a chemotherapeutic agent, crosses the blood‒brain barrier and induces cognitive deficits and structural brain alterations. This study aimed to assess the dose-dependent neurotoxic effects of cisplatin on rat brain and hippocampal tissues via behavioural, histopathological, and immunohistochemical evaluations. Thirty-eight Wistar albino rats (60 days old) were divided into four groups: control (n = 8), cisplatin 5 mg/kg (n = 10), cisplatin 7.5 mg/kg (n = 10), and cisplatin 12 mg/kg (n = 10). The control group received saline, while the experimental groups received a single intraperitoneal dose of cisplatin. Behavioral experiments were conducted 24 h post-injection, and after three days, the rats were euthanized. Brain and hippocampal tissues were harvested for histopathology and immunohistochemistry. Compared with the control group, the cisplatin-treated groups presented significant weight loss (p < 0.001). Behavioural experiments revealed dose-dependent impairments in short- and long-term memory. Histopathological examination revealed increased neuronal necrosis/apoptosis, neuronophagia, gliosis, hyperemia, and perivascular edema, with greater severity at higher doses. These changes were most pronounced in the cisplatin 7.5 mg/kg and 12 mg/kg groups (p < 0.05), whereas the cisplatin 5 mg/kg group showed an increased severity of all symptoms except for hyperemia. Immunohistochemical staining revealed no significant changes in the Bax/Bcl-2 ratio at cisplatin 5 mg/kg, and significant increases were observed at cisplatin 7.5 mg/kg and 12 mg/kg (p < 0.05). Glial fibrillary acidic protein (GFAP) expression increased significantly in the cerebral cortex and hippocampus, especially at the highest dose. Cisplatin-induced toxicity resulted in dose-dependent increases in weight loss, neuronal necrosis/apoptosis, neuronophagia, gliosis, and perivascular edema, with significant increases in the Bax/Bcl-2 ratio and GFAP expression at cisplatin 7.5 mg/kg and 12 mg/kg, suggesting that these doses are optimal for studying neurotoxicity.