Abstract:Background: Acute ischemic stroke (AIS) is a brain medical disorder characterized by the sudden loss of blood circulation to an area of the brain, resulting in a loss of its neurologic function. Cerebrolysin is a mixture of neuropeptides and free amino acids. Aim of the work: This study aimed to evaluate the role of cerebrolysin in ameliorating the histological,immunohistochemical and biochemical harm in post ischemic stroke and also to assess its dose dependent effect. Materials and Methods: Thirty adult male rats were divided into 3 equal groups; control, ischemic and post ischemic treated groups. After dissecting hippocampal dentate gyrus prepared sections were stained with ematoxylin and eosin, Erβ and calretinin proteins. Oxidative stress parameters, TNF α, and HSP-70 assay. Also, Gh receptor gene expression and DNA fragmentation test were measured. Immunoperoxidase reactions for GFAPin astrocyte was estimated. Statistical analysis was conducted. Results: Ischemia group showed decrease number of granule cells with small dark stained nuclei, areas of cell loss and numerous spindle shaped cells in the sub-granular zone. A faint positive immunoreaction for ERβ in nuclei of granular cells and negative reaction for calretinin was detected in granule cells. Antioxidant enzymes in the brain tissue as MDA,TNF α and HSP-70 were significantly elevated in ischemic group compared to control and post ischemic treated groups. Gh receptor gene were decreased, while Fragmentation index of DNA was significantly increased. Administration of 2.5 mg/kg cerebrolysinshowed partial improvement, whereas, 5 mg/kg dose displayed more ameliorative effects. Increased GFAP immune-expression in the cytoplasm of astrocytes in ischemic group compared to control and post ischemic treated groups Conclusion: Cerebrolysin was effective in experimentally induced AIS (Acute ischemic stroke) in a dose-dependent manner as proved by improving the histological structure, immunohistochemical reactions and biochemical parameters of the dentate gyrus of hippocampus in adult male albino rats.