en Neurophysiology/Pharmacology Neurophysiology/Pharmacology Experimental research article Experimental research article <div style="text-align: justify;"><span style="font-size:12px;"><span style="font-family:Arial;"><strong>Introduction:</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.<br /> <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. Neurological deficits were assessed using the Garcia scale 7 days after ischemia. Neuronal cell death was evaluated using cresyl violet staining. We examined gene and protein levels of BDNF, NLRP3, and NMDAR in brain tissue using real-time PCR and immunohistochemistry. TTC staining was used to determine cerebral infarct volume in brain tissue, and ELISA tests to measure IL-1&beta; and IL-18 levels.<br /> <strong>Results: </strong>Cresyl violet staining demonstrated that glutamic acid+exosomes significantly reduced neuronal degeneration. Garcia&rsquo;s test results showed that glutamic acid, independently or in combination with exosomes, significantly improved sensory and motor functions. The results of IHC and Real-Time PCR 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.<br /> <strong>Conclusion: </strong>The use of glutamic acid with SH-SY5Y neuroblastoma-derived exosomes exerts neuroprotective benefits by enhancing neurotrophic factors and diminishing apoptosis in the MCAO model.</span></span></div> Brain Ischemia, Glutamic Acid, Exosomes, NLRP3 Inflammasome, Caspase, 168 184 http://ppj.phypha.ir/browse.php?a_code=A-10-2519-1&slc_lang=en&sid=1 Mehrshad Mohammadzadeh mehrshadapid@yahoo.com 3200319475328460039551 3200319475328460039551 No Department of Pharmacology, Ka.C., Islamic Azad University, Karaj, Iran Zohreh Abdolmaleki Zohreh.abdolmaleki@iau.ac.ir 3200319475328460039552 0000000320165753 Yes Department of Pharmacology, Ka.C., Islamic Azad University, Karaj, Iran Ali Karimi Goudarzi Ali.Karimi@iau.ac.ir 3200319475328460039553 3200319475328460039553 No Department of Physiology, Ka.C., Islamic Azad University, Karaj, Iran Seyed mohammadreza Bolandi Mreza.bolandi@gmail.com 3200319475328460039554 3200319475328460039554 No Department of Pharmacology, Ka.C., Islamic Azad University, Karaj, Iran