Promising Potential of Edaravone-Loaded Nanogel in Ameliorating of Stroke in Rats: The Modulation of Immune Response.

OBJECTIVES: Ischemic stroke is mainly caused by the interruption of cerebral blood flow, which causes severe neurological damage and is one of the main drawbacks of death and disability worldwide. Edaravone (EDV) has been clinically used for the treatment of ischemic stroke in Japan and some countries with two major drawbacks: poor water solubility and nephrotoxicity. Therefore, GSH-PMAA or nanogel was utilized as a drug carrier for EDV to overcome this issue. METHODS: The study was designed to assess the cognitive response and expression of brain tissue genes, including heat-shock protein (Hsp70), Toll-like receptors (Tlr4&Tlr7), following treatment with EDV-loaded nanogel or GSH-PMAA-EDV in ischemic rats. Animals were randomly divided into seven groups, and after the induction of the ischemia-like model, rats received different doses of EDV-loaded nanogel. RESULTS: On the day after the novel object recognition test, the rodent hippocampus was dissected and used for the evaluation of gene expression. Real-time PCR was used to evaluate the gene expression of Tlr4, Tlr7, and Hsp70. These results indicated that after the induction of stroke in animals, the expression of Tlr4 and Tlr7 increased significantly. However, no significant change in Hsp70 expression was observed. However, EDV-loaded nanogel at doses of 20, 40, and, 250 μg/kg restored the overexpression of Tlr4 and Tlr7. CONCLUSION: Treatment with EDV-loaded nanogel has been shown to improve cognitive behavior and immune response of neural tissue in a transient global ischemic model. These improvements were also achieved at lower equalized doses when compared with the unmodified EDV.