en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Astrocyte dysfunction plays a crucial role in epileptogenesis by impacting neuronal excitability and synaptic transmission. This study investigates how specific small molecules (SMs) affect the survival of astrocytes derived from various brain regions (the neocortex, hippocampus, or amygdala) of patients with medically refractory epilepsy.<br> <strong>Methods</strong>: This study evaluated astrocyte responses to three distinct SMs (valproate, forskolin, and GSK3 inhibitor/WNT activator CHIR99021), individually or in combined forms, to determine their differential effects on astrocyte survival.&nbsp;<br> <strong>Results</strong>: The effects of SMs on astrocyte survival varied based on the brain tissue source and individual patient differences. Astrocytes from the amygdala of two patients showed heightened sensitivity to the SMs, while astrocytes from the neocortex of one patient exhibited decreased viability following treatment with CHIR99021 and valproate. Moreover, astrocytes from the hippocampus exhibited a significant decrease in viability in one patient, whereas no significant changes were observed in other patients.&nbsp;<br> <strong>Conclusion</strong>: Variability in astrocyte responses to SMs, influenced by brain region and patient differences, may highlight their role in shaping diverse therapeutic outcomes in individuals. Further studies are required to clarify the factors involved in the different behaviors of astrocytes in response to SMs in epilepsy.</div> Small molecule (SM), Neuroglia, Seizure, Cell proliferation, Treatment outcomes 751 762 http://bcn.iums.ac.ir/browse.php?a_code=A-10-5446-3&slc_lang=en&sid=1 Javad Momeni javad.epost@gmail.com 13700319475328460054973 13700319475328460054973 No Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Elham Hosseini lhamhosseini@gmail.com 13700319475328460054974 13700319475328460054974 No Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Maryam Khaleghi Ghadiri maryam.khaleghi@ukmuenster.de 13700319475328460054975 13700319475328460054975 No Department of Neurosurgery, Münster University, Münster, Germany. Fariborz Samini saminif@mums.ac.ir 13700319475328460054976 13700319475328460054976 No Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Alireza Tabibkhooei tabibkhooei.a@iums.ac.ir 13700319475328460054977 13700319475328460054977 No Department of Neurosurgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Ali Gorji gorjial@uni-muenster.de 13700319475328460054978 13700319475328460054978 No Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Sajad Sahab Negah SahabNegahS@mums.ac.ir 13700319475328460054979 13700319475328460054979 Yes Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.