en Neurophysiology/Pharmacology Neurophysiology/Pharmacology Experimental research article Experimental research article <span style="font-size:12px;"><span style="font-family:Arial;"><span style="line-height:150%"><span style="line-height:150%"><span new="" roman="" times=""><strong>Introduction/Background:</strong> Ischemic stroke and brain trauma are significant causes of death and disability in the West. Inflammasomes induce pro-inflammatory cytokine production in cerebral ischemia, thereby driving inflammation. The current study investigates the effects of glutamic acid, N-methyl-D-aspartate receptor agonist, and SH-SY5Y Neuroblastoma-Derived Exosomes in the rat model of cerebral ischemia. </span></span></span><br /> <span style="line-height:150%"><span style="line-height:150%"><span new="" roman="" times=""><strong>Methods:</strong> Sixty adult male Wistar rats were randomly assigned to five groups. After MCAO, rats were treated with glutamic acid, SH-SY5Y neuroblastoma-derived exosomes, and both. The Garcia scale measured neurological damage 7 days after ischemia. We counted cell deaths in the brain using crystal violet staining. We examined gene and protein levels of BDNF, NLRP3, and NMDAR in brain tissue using real-time PCR and immunohistochemistry. The study used TTC staining to determine infarct cell volume in brain tissue, and ELISA tests to measure IL-1&beta; and IL-18 levels. </span></span></span><br /> <span style="line-height:150%"><span style="line-height:150%"><span new="" roman="" times=""><strong>Results:</strong> Cresyl violet staining demonstrated that glutamic acid+exosomes substantially reduced neurodegeneration. Garcia&rsquo;s test results showed that glutamic acid, independently or in combination with exosomes, significantly enhanced the function of sensory and movement regions. The results clearly indicated that the expression of the BDNF gene and protein, as well as the NMDAR gene, increased, whereas the expression of the NLRP3 gene and protein, and the Caspase-1 protein, decreased. ELISA results showed a significant drop in IL-1&beta; and IL-18 levels in MCAO groups treated with glutamic acid, exosomes, or both.&nbsp; </span></span></span><br /> <strong>Conclusion:</strong> The use of glutamic acid with SH-SY5Y nueroblastoma-derived exosome exerts neuroprotective benefits by enhancing neurotorophic factors and diminishing apoptosis in the MCAO model.&nbsp;<br /> &nbsp;</span></span> Brain Ischemia,Glutamic Acid,Exosomes,NLRP3 Inflammasome,Caspase-1 0 0 http://ppj.phypha.ir/browse.php?a_code=A-10-2519-1&slc_lang=en&sid=1 Mehrshad Mohammadzadeh mehrshadapid@yahoo.com 3200319475328460038768 3200319475328460038768 No Department of Pharmacology, Ka.C., Islamic Azad University, Karaj, Iran Zohreh Abdolmaleki Zohreh.abdolmaleki@iau.ac.ir 3200319475328460038769 3200319475328460038769 Yes Department of Pharmacology, Ka.C., Islamic Azad University, Karaj, Iran Ali Karimi Goudarzi Ali.Karimi@iau.ac.ir 3200319475328460038770 3200319475328460038770 No Department of Physiology, Ka.C., Islamic Azad University, Karaj, Iran Seyed mohammadreza Bolandi Mreza.bolandi@gmail.com 3200319475328460038771 3200319475328460038771 No Department of Pharmacology, Ka.C., Islamic Azad University, Karaj, Iran