Background: Pyrethroids pose health risks to humans. Therefore, it is imperative to assess the preventive
benefits of thymoquinone against neurotoxicity induced by cypermethrin- in the hippocampal dentate
gyrus. Methods: Forty male adult Wistar rats with an average weight of 180-200g were randomly allocated
to five (5) groups, and each comprising eight rats (n=8 per group). The groups were designated
as follows, through oral administrations for 14 days: 0.5ml phosphate- buffered saline (PBS) was given
to group one; Group two received 20mg/kg of cypermethrin (CYM); Group three received 10 mg/kg of
thymoquinone (THQ); Group four received 20 mg/kg of cypermethrin followed by 10mg/kg of thymoquinone
(CYM-10mgTHQ); and Group five received 20 mg/kg and 5mg/kg cypermethrin and thymoquinone
respectively (CYM-5 mgTHQ). Behavioral, histological, immunohistochemical, and biochemical analyses
were conducted post-treatment. Results: Cypermethrin administration caused the rise in pro-inflammatory
cytokine TNF-α, Nuclear Factor-kappa B (NF-κB) and increased expression of astrocytes, microglia, and
pro-apoptotic protein Bax. Additionally, cypermethrin reduced levels of anti-inflammatory cytokine IL-10
and acetylcholinesterase (AChE) activity. Cytoarchitectural disruption of dentate gyrus were observed.
Cognitive deficits were evident. Thymoquinone treatment attenuated TNF-α and NF-κB elevation, reduced
astrocyte, microglial, and Bax expression, and increased IL-10 and AChE. Conclusion: Thymoquinone
demonstrated anti-inflammatory and anti-apoptotic effects against cypermethrin-induced neurotoxicity,
improving cognitive function in rats.