Insights into Parkinson’s Disease Pathology Focusing on Glial Response and Apoptosis in a Classic Rat Model of Dopaminergic Degeneration

Background/Objectives: Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc). Experimental models that replicate core features of PD are critical to investigate underlying mechanisms and therapeutic strategies. Here we evaluated the effects of an acute unilateral intrastriatal lesion induced by 6-hydroxydopamine (6-OHDA) on neuronal loss and the associated inflammatory response. Methods: Adult male Wistar rats received an injection of 6-OHDA into the right striatum, while the contralateral side received vehicle. Motor behavior was assessed by cylinder and open field tests on post-lesion days (PLDs) 7 and 14. Brains were analyzed by immunohistochemistry for tyrosine hydroxylase (TH), glial response (GFAP and Iba1), and caspase-3 at PLD +14. Results: A marked reduction in TH-immunoreactivity in the lesioned striatum was observed, with ~40% loss of TH-positive neurons in the ipsilateral SNpc. Surviving neurons displayed a 28% increase in soma size compared to the contralateral side. The lesion was accompanied by robust astrocytic and microglial activation at the injection site, as well as enhanced GFAP immunoreactivity in the ipsilateral SN pars reticulata. Apoptotic profiles emerged in the SNpc at PLD +14. Functionally, these alterations were reflected in significant motor asymmetry and decreased locomotor activity. Conclusions: Our findings demonstrate that neuroinflammation accompanies early dopaminergic degeneration following intrastriatal 6-OHDA administration, contributing to motor deficits. Future studies with older animals and broader behavioral and anatomical assessments—including regions such as the ventral tegmental area and motivational or anxiety-related paradigms—may enhance translational relevance.