en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <strong>Introduction</strong>: Sodium valproate (VPA) is widely used to treat neurological disorders. This study aimed to investigate the spatial arrangement and three-dimensional structure of the hippocampal CA1 region, as well as the biochemical changes in the brains of ischemic rats.&nbsp;<br> <strong>Methods</strong>: Thirty male rats were randomly assigned to three groups: Sham, middle cerebral artery occlusion (MCAO), and MCAO + VPA. The right common carotid artery was ligated for one h. On days 0&ndash;3 of reperfusion, animals received intraperitoneal (IP) injections of VPA (300 mg/kg). One week after MCAO, the brains (ischemic hemisphere) of five animals were removed and fixed for structural (stereological) studies. In addition, the ischemic hemispheres of five other rats were removed for malondialdehyde (MDA) assay.&nbsp;<br> <strong>Results</strong>: Our data demonstrated that VPA significantly restored the hippocampal spatial arrangement of pyramidal neurons, reduced three-dimensional deformation, and decreased the total number of dead neurons and MDA levels induced by MCAO.&nbsp;<br> <strong>Conclusion</strong>: This study indicates that reduced neuronal loss in the CA1 region, along with improvements in spatial cell arrangement and three-dimensional structure, may be correlated with reduced levels of oxidative stress. These structural alterations may contribute to the behavioral effects previously reported, including those in our earlier studies. Focal cerebral ischemia, Sodium valproate (VPA), Hippocampus, Oxidative stress 1159 1168 http://bcn.iums.ac.ir/browse.php?a_code=A-10-7531-1&slc_lang=en&sid=1 Masoud Haghani haghani@sums.com 13700319475328460056654 13700319475328460056654 No Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Mohammad Reza Namavar namavarm@sums.ac.ir 13700319475328460056655 13700319475328460056655 No Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Farzaneh Dehghani dehghanf@sums.ac.ir 13700319475328460056656 13700319475328460056656 No Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Jafar Vatanparast naseh@sums.ac.ir 13700319475328460056657 13700319475328460056657 No Department of Biology, Faculty of Science, Shiraz University, Shiraz, Iran. Zahra Naseh zhrnaseh65@gmail.com 13700319475328460056658 13700319475328460056658 No Department of Laboratory Medicine and Pathology, Center for Transfusion Medicine and Cellular Therapies, School of Medicine, Emory University, Atlanta, United States. Samira Panahi Kokhdan panahis1368@gmail.com 13700319475328460056659 13700319475328460056659 No Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Maryam Naseh naseh@sums.ac.ir 13700319475328460056660 13700319475328460056660 Yes Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.