Objective: In the present study, we examined neuroprotective effects, if any, of IBD drug, a  inhibitor of the phosphodiesterase IV in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting about 2% of the population over 65 years of age. Ibudilast (IBD), a  inhibitor of the phosphodiesterase IV (PDE IV),  has recently been shown to exert neuroprotective effects in an stroke and Alzheimer transgenic mouse model and in hypoxic-ischemic damage in the rat brain.

Method: Experimental animal is muscular weighing 25–35 g of 3–4-month-old. The drug was given four times at 12 h intervals by gavation (10–50 mg/kg) in animals made parkinsonian following two doses of MPTP (30 mg/kg, i.p.) injection for 10 consecutive days. Control mice were injected with the same volume of pure DMSO. Brain was used for biochemical and histopathological study for glial cell-derived neurotrophic factor (GDNF). Evaluation concerned dopamine content in the striatum, tyrosine hydroxylase (TH) protein and α-synuclein, TNF-α, IL-6, and IL-1β  expression measured in both control and treatment group.

Results: MPTP-induced striatal dopamine depletion  was significantly attenuated by higher dose of IBD. MPTP-induced catalepsy and akinesia, as well as loss in swim ability, were blocked dose-dependently by IBD. These results indicate that the observed neuroprotective effects of IBD from its significant antioxidant and anti-neuro inflammatory action. Our study demonstrated that chronic administration of IBD attenuated astroglial reactivity and increased GDNF production in the striatum. Moreover, IBD reduced TNF-α, IL-6, and IL-1β expression.  It also prevented TH protein decrease and increased α-synuclein level in treated rats.

Conclusion: Present data show a neuroprotective effect of the PDE IV specific inhibitor IBD against dopaminergic neuron degeneration, suggesting that PDE IV inhibitors might be a potential treatment for Parkinson’s disease. Diminished inflammation and an increased level of GDNF may provide a better outcome in the later stages of neurodegeneration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotective-effects-of-ibudilast-a-phosphodiesterase-iv-inhibitor-in-mouse-model-of-parkinsons-disease/