Objective: This research aims to assess whether Ibudilast (IBD), a phosphodiesterase IV (PDE IV) inhibitor, can mitigate the damage induced by 3-nitropropionic acid (3-NP) in a rat model of HD.

Background: Huntington’s disease (HD) is a genetic disorder where neurons in certain brain regions gradually deteriorate and die, affecting voluntary movement and other functions.

Method: A total of 80 male Sprague-Dawley rats, aged 3 to 4 months, were given oral pretreatment with Ibudilast (IBD) at doses of 50 and 100 mg/kg body weight before being administered 3-nitropropionic acid (3-NP) intraperitoneally (i.p.) at a dose of 12 mg/kg body weight for 15 days. Nimodipine (12 mg/kg, orally) was used as a positive control drug. Changes in body weight, grip strength, and behavior were monitored on the 5th, 10th, and 15th days after 3-NP treatment. At the end of the study, various behavioral tests were conducted, including beam walk, rotarod, and grip strength assessments. The levels of antioxidant enzymes (such as reduced glutathione, superoxide dismutase, catalase), malondialdehyde, brain-derived neurotrophic factor, and cyclooxygenase-2 (COX-2), as well as alterations in neurotransmitters (gamma-aminobutyric acid, dopamine, norepinephrine, acetylcholine), were analyzed in the rat model of Huntington’s disease.

Results: The findings reveal that the administration of 3-NP led to a notable decrease in body weight, memory function, grip strength, and locomotion activity, accompanied by a significant increase in oxidative stress levels, COX-2 expression, and inducible iNOS expression. However, the group treated with IBD demonstrated a significant restoration of memory function through the modulation of behavioral activities. Animals treated with IBD exhibited marked improvements in behavioral, biochemical, and histological parameters compared to those treated solely with 3-NP. Additionally, the results indicate that IBD effectively mitigated 3-NP-induced changes in behavioral, biochemical, and neurotransmitter levels in a dose-dependent manner.

Conclusion: These findings provide clear evidence of the neuroprotective, neurotrophic, and memory-enhancing effects of IBD as a therapeutic agent for managing HD pathology in a rat model.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ibudilast-a-phosphodiesterase-inhibitor-alleviates-huntingtons-disease-pathology-through-neuroinflammation-modulation-and-signaling-pathway-regulation-in-a-rat-model/