Aslanlar_2026_Open.Med.(Wars)_21_20261406

OBJECTIVES: To investigate the neuroprotective effects of adalimumab against cisplatin-induced cognitive impairment (CICI) and to evaluate its potential to ameliorate anxiety- and depression-like behaviors as well as learning and memory deficits through modulation of Tumor necrosis factor-alpha (TNF-alpha)-mediated neuroinflammation, cholinergic homeostasis, and apoptosis. METHODS: Adult male Wistar rats were divided into four groups (n=6/group): Control, Cisplatin (2 mg/kg/day, i.p., 10 days), ADA (10 mg/kg, i.p., three doses), and Cisplatin + ADA. Anxiety-, depression-like behaviors and memory performance were assessed using the open field test, elevated plus maze, forced swim test, and novel object recognition test. Serum and hippocampal TNF-alpha, nitric oxide (NO), acetylcholinesterase (AChE), acetylcholine (ACh), and p53 levels were measured by ELISA. RESULTS: Cisplatin induced anxiety- and depression-like behaviors and impaired recognition memory without affecting locomotor activity. These behavioral alterations were accompanied by increased TNF-alpha, NO, AChE, and p53 levels in the hippocampus. ADA treatment significantly reversed behavioral deficits and normalized inflammatory, cholinergic, and stress-related markers. CONCLUSIONS: Adalimumab attenuates cisplatin-induced cognitive and mood disturbances, likely through modulation of TNF-alpha-mediated neuroinflammation, cholinergic imbalance, and stress-related signaling pathways.