Wheat Germ Agglutinin as a Treatment for Traumatic Brain Injury

Abstract

Traumatic brain injury continues to be the leading cause of persistent neurological disorders, with secondary damage caused by chronic neuroinflammation playing a key role in their development. After the initial mechanical action, a cascade of pathological reactions is triggered: microglia are activated, peripheral immune cells infiltrate, which supports long-term inflammatory signaling. These processes lead to the death of neurons, disruption of synaptic transmission, and the formation of persistent cognitive deficits. In this regard, approaches that can both regulate post-traumatic immune responses and increase the effectiveness of delivering therapeutic agents to the brain are becoming particularly relevant. Wheat germ agglutinin is a plant lectin characterized by high affinity for glycoconjugates containing N‑acetylglucosamine and sialic acid. It is known that it is resistant to proteolysis, is able to penetrate the intestinal barrier and accumulate on the vascular endothelium. Previous studies have demonstrated that WGA can enhance the transport of nanoparticles across the blood-brain barrier, as well as improve behavioral performance in models of neurodegenerative diseases. At the same time, its possibilities in terms of modulating post-traumatic inflammation and promoting recovery after TBI have not been studied to date. Wheat germ agglutinin (WGA) was isolated from wheat germ and analyzed by both dot blot and SDS-PAGE. Extraction of WGA using imidazole increased the amount of WGA that could be detected compared to untreated crude extract. While the cytotoxic assay revealed that the treated group cells were slightly less viable than the control group, the percentage of cell viability was not significantly altered by the WGA treatment across the tested concentrations. After WGA treatment, TBI mice performed better on the Barnes maze than did the untreated TBI mice group. This was indicated by a decreased latency time to locate the escape chamber during testing. Additionally, WGA treated TBI mice showed evidence of the lectin in the brains. In the RAW 264.7 macrophage cell line, the lectin upregulated expression of both Nos2 and TNF, without increasing Arg1 expression. This may be evidence of an M1 phenotype shift. Overall, these results suggest that the potential WGA mechanism of action may involve a combination of brain penetration, modulation of macrophage phenotype, and reduced cognitive decline following TBI in mice. Further investigation into WGA treatment will be required in order to define mechanism of action, dosage regimen, and safety profile.