Introduction Lipopolysaccharide (LPS) induces neuronal injury by stimulating microglia, which release pro-inflammatory markers and neurotoxic factors. Folate deficiency induces microglial activation and modulates nuclear factor-κB (NF-κB) p65 and neurogenic locus Notch homolog protein 1 (Notch1) expression in the hippocampus. This study investigated the neuroprotective effect of folic acid against LPS-induced neurotoxicity in rats, focusing on its modulation of microglial activation and the Notch1, NF-κB, and p65 signaling pathways. Methods A total of 24 Sprague–Dawley male rats were assigned to four groups: control, folic acid, LPS, and folic acid + LPS. After sacrifice, the left cerebral hemisphere was subjected to histopathological assessment using hematoxylin and eosin (HE) staining and immunohistochemical assessment using anti-GFAP, anti-Iba1, anti-cyclooxygenase-2 (COX-2), anti-tumor necrosis factor- α (TNF-α), and anti-NF-κB antibodies. The hippocampus was extracted from the right hemisphere and used to assess the gene expression of Notch1, TNF-α, interleukin-6 (IL-6), and COX-2 markers using real-time reverse transcription PCR. Results Folic acid ameliorated LPS-induced neuronal damage in the hippocampus, suppressed microglial activation (GFAP and Iba-1), downregulated Notch1 and NF-κB p65, and improved neuroinflammatory responses (TNF-α, IL-6, and COX-2), regardless of the region. Conclusion Folic acid exerted an equivalent neuroprotective effect in both the CA1 and CA3 regions by suppressing microglial activation and modulating the Notch1/NF-κB signaling pathway, thereby reducing neuroinflammation. These findings suggest that folic acid may serve as a potential adjuvant neuroprotective agent against inflammation-mediated neuronal injury.
El-kader et al. (Fri,) studied this question.