Faculty, Staff and Student Publications
Publication Date
11-22-2024
Journal
Cell Death & Disease
Abstract
Levodopa (L-DOPA) treatment is a clinically effective strategy for improving motor function in patients with ischemic stroke. However, the mechanisms by which modulating the dopamine system relieves the pathology of the ischemic brain remain unclear. Emerging evidence from an experimental mouse model of ischemic stroke, established by middle cerebral artery occlusion (MCAO), suggested that L-DOPA has the potential to modulate the inflammatory and immune response that occurs during a stroke. Here, we aimed to demonstrate the therapeutic effect of L-DOPA in regulating the systemic immune response and improving functional deficits in mice with ischemia. Transient MCAO led to progressive degeneration of nigrostriatal dopamine neurons and significant rotational behavior in mice. Exogenous L-DOPA treatment attenuated the striatonigral degeneration and reversed motor behavioral impairment. Notably, treatment with L-DOPA significantly increased IL-13 but reduced IFN-γ in infarct lesions. To investigate the role of IL-13 in motor behavior, we stereotaxically injected anti-IL-13 antibodies into the infarct area of the mouse brain one week after MCAO, followed by L-DOPA treatment. The intervention reduced dopamine, IL-13, and IL-10 levels and exacerbated motor function. IL-13 is potentially expressed on CD4 T cells, while IL-10 is mainly expressed on microglia rather than astrocytes. Finally, IL-13 activates the phagocytosis of microglia, which may contribute to neuroprotection by eliminating degenerating neurons. Our study provides evidence that the L-DOPA-activated dopamine system modulates peripheral immune cells, resulting in the expression of anti-inflammatory and neuroprotective cytokines in mice with ischemic stroke.
Keywords
Animals, Levodopa, Interleukin-13, Neuroprotective Agents, Mice, Male, Mice, Inbred C57BL, Brain Ischemia, Infarction, Middle Cerebral Artery, Striatonigral Degeneration, Disease Models, Animal, Microglia, Dopaminergic Neurons, Neurological disorders, Cell death in the nervous system
DOI
10.1038/s41419-024-07252-x
PMID
39578419
PMCID
PMC11584695
PubMedCentral® Posted Date
11-22-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes