Muthuraman_2026_Iran.J.Pharm.Res_25_e166629

BACKGROUND AND OBJECTIVE: The present study investigated the effect of folic acid in a rat model of sciatic nerve injury (SNI)-induced cognitive dysfunction. METHODS: In this study, six groups with six male Wistar rats in each group were used. The simple randomization method was adopted for unbiased assignment of animals based on age, sex, and weight variations. Folic acid (10 and 20 mg/kg) and donepezil (1 mg/kg) were administered by the oral (p.o.) route for 10 days. The rats' cognition was assessed by the Morris water maze (MWM) test. The assessment of the learning trial (acquisition) was the escape latency time (ELT), while the assessment of memory retention (retrieval) was the time spent in the target quadrant (TSTQ), which was measured in the MWM test. The brain samples of rats were used to assess biomarkers such as total protein, reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and acetylcholinesterase (AChE) activity. The behavioral data were statistically analyzed by a two-way analysis of variance (ANOVA) test, and biomarkers were analyzed by one-way ANOVA. The 95% confidence level (P < 0.05) was fixed for confirmation of statistical significance. RESULTS: The administration of folic acid statistically (P < 0.05) reduced the SNI-induced elevated ELT and TSTQ levels compared to the sham control group. However, folic acid also prevented the rise in TBARS and AChE activity and the drop in GSH after SNI. The comparable outcomes were statistically (P < 0.05) similar to those of the donepezil-administered group. CONCLUSIONS: Folic acid has great potential to be used in treating peripheral nerve injury-associated cognitive dysfunction.