The Activation of Microglia and the Generation of Reactive Oxygen Species Induced by Medial Forebrain Bundle Axotomy

Background: We endeavored to examine the impact of reactive oxygen species (ROS) on the degeneration of dopaminergic neurons by employing the medial forebrain bundle (MFB) axotomy model, a recognized animal model of Parkinson’s disease. Methods: The MFB of Wistar rats was lesioned and animals were sacrificed at 7, 14 and 28 days post-lesion for immunofluorescent staining. Additionally, in some experimental animals, hydroethidine was injected into the abdominal cavity 30 minutes before sacrifice to examine the presence of ROS within the brain tissue and characterize the cell types responsible for their generation throughout the pathological progression. Result: At 7 days post-surgery, an excessive accumulation of activated microglia was observed in the ipsilateral substantia nigra (SN) using antibodies OX42 and OX6, indicating their strong immunopositive reaction. Although the reactivity decreased somewhat in the 14-day and 28-day groups compared to the 7-day group, a significant number of activated microglia still congregated. Additionally, these cells exhibited strong immunopositive reactions to ED1, indicating their active phagocytic activity. Furthermore, many activated microglia showing positive reactions in OX6 immunofluorescent staining simultaneously exhibited ethidium fluorescence activity, indicating their vigorous generation and secretion of ROS.