Sex-Specific Neuroinflammation and Apoptotic Outcomes in the Cerebellum of Wistar Rats Exposed to λ-Cyhalothrin

Sex-related biological differences influence how the nervous system responds to toxic exposures. These differences may determine the severity and pattern of neuronal injury produced by environmental neurotoxicants such as insecticides. λ-Cyhalothrin (LCT), a widely used type II pyrethroid, has been associated with neurotoxicity through mechanisms involving oxidative stress, neuronal damage, and neuroinflammation. This study investigated sex-specific differences in cerebellar toxicity following exposure to LCT in Wistar rats. Forty-eight adult rats (24 males and 24 females) were divided into control, low-dose (2 mg/kg), and high-dose (4 mg/kg) groups and treated orally for ten consecutive days. Neuromuscular performance was assessed using the hanging wire test. Cerebellar cytoarchitecture was evaluated using hematoxylin and eosin staining, while neuroinflammatory responses and glial integrity were assessed through immunohistochemical detection of tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule-1 (Iba1). Male rats showed no significant change in forelimb strength, whereas females demonstrated reduced latency to fall following lowdose exposure. Immunohistochemical analysis revealed increased activation of microglia and astrocytes in males, particularly at the lower dose, indicating an early neuroinflammatory response. In contrast, female rats exhibited limited glial activation but showed a dose-dependent increase in TNF-α expression within the cerebellum. These findings indicate that male rats display greater susceptibility to LCT-induced cerebellar neurotoxicity through glial activation, whereas females demonstrate a different inflammatory profile. The results highlight the importance of considering sex as a biological variable when assessing the neurotoxic effects of pesticides.

Key Words: λ-cyhalothrin, neurotoxicity, sex differences, cerebellum, neuroinflammation