Natural Antioxidants in Dementia

Cabezas, Ricardo; Avila, Marco Fidel; Torrente, Daniel; González, Janneth; El-Bachá, Ramon dos Santos; Guedes, Rubem Carlos Araújo; Barreto, George E.

doi:10.1016/b978-0-12-407824-6.00076-8

Cited by 3 publications

(1 citation statement)

References 56 publications

(115 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If dopaminergic signaling in LID subjects causes an increase in striatal CBF, this would result in greater Ldopa delivery through the blood supply. Importantly, the blood-brain barrier is disrupted in PD, even independently of apparent angiogenesis, 6,33,34 and may be particularly disrupted in LID subjects. Increased cerebral blood flow could therefore result in greater unregulated L-dopa transmission into the striatal microenvironment, resulting in increased DA flux responsible for LID symptoms, as well as further reinforcing astrocyte-mediated CBF increases in a positive feedback loop.…”

Section: Discussionmentioning

confidence: 99%

The Vasomotor Response to Dopamine Is Altered in the Rat Model of l‐dopa‐Induced Dyskinesia

et al. 2020

View full text Add to dashboard Cite

A BS TRACT: Background: Levodopa (L-dopa) is the frontline treatment for motor symptoms of Parkinson's disease. However, prolonged use of L-dopa results in a motor complication known as levodopa-induced dyskinesia (LID) in~50% of patients over 5 years. Objectives: We investigated neurovascular abnormalities in a rat model of LID by examining changes in angiogenesis and dopamine-dependent vessel diameter changes. Methods: Differences in striatal and nigral angiogenesis in a parkinsonian rat model (6-OHDA lesion) treated with 2 doses of L-dopa (saline, 2, and 10 mg/kg/day subcutaneous L-dopa treatment for 22 days) by 5-bromo-2'deoxyuridine (BrdU)-RECA1 co-immunofluorescence. Difference in the vasomotor response to dopamine was examined with 2-photon laser scanning microscopy and Dodt gradient imaging. Results: We found that the 10 mg/kg L-dopa dosing regimen induced LID in all animals (n = 5) and induced significant angiogenesis in the striatum and substantia nigra. In contrast, the 2 mg/kg treatment induced LID in 6 out of 12 rats and led to linearly increasing LID severity over the 22-day treatment period, making this a promising model for studying LID progression longitudinally. However, no significantly different level of angiogenesis was observed between LID versus non-LID animals. Dopamine-induced vasodilatory responses were exaggerated only in rats that show LID-like signs compared to the rest of groups. Additionally, in juvenile rats, we showed that DA-induced vasodilation is preceded by increased Ca 2+ release in the adjacent astrocytes. Conclusion: This finding supports that astrocytic dopamine signaling controls striatal blood flow bidirectionally, and the balance is altered in LID.

show abstract

Section: Discussionmentioning

confidence: 99%