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Dimethyl fumarate attenuates 2-VO-induced vascular dementia via activating the Nrf2 signaling pathway in rats

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Abstract

Background

Chronic cerebral hypoperfusion (CCH) induced oxidative stress and inflammation is known to be implicated in the pathogenesis of vascular dementia. The nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a potential therapeutic target for neuroprotection. In the present study, we investigated the beneficial effects of dimethyl fumarate (DMF), an Nrf2 activator in an experimental model of vascular dementia.

Methods

Permanent occlusion of the bilateral common carotid arteries (2-VO) was performed to induce CCH in adult male Sprague–Dawley rats. DMF (15, 30, and 60 mg/kg) was administered for 4 weeks. Cognitive performance was assessed using the Morris water maze (MWM) and novel object (NOR) tests. After behavior tests, various oxidative and inflammatory markers were assessed in the hippocampus.

Results

The obtained results indicate that treatment with DMF significantly improved 2 VO-induced cognitive deficits. DMF decreased MDA (p < 0.001), protein carbonyl (PCO) contents (p < 0.001), and acetylcholinesterase (p < 0.01) activities, and inhibited inflammatory markers (TNF-α, IL-1β, NF-κβ, and COX-2) levels. Furthermore, our results showed that DMF augmented GSH (p < 0.001) levels and SOD (p < 0.05), CAT, and GSH-Px (p < 0.001) activities in the hippocampus. Nrf2 (p < 0.05) and its downstream targets HO-1 levels (p < 0.01) and NQO1 (p < 0.05) levels were also up-regulated after DMF treatment.

Conclusion

Taken together, the results demonstrate that DMF could serve as a promising neuroprotective agent for treating vascular dementia.

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Funding

This experimental work did not receive any specific grant from any funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Pharmacology Research Laboratory, Pharmacology Division, UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India

    Navneet Dhaliwal, Jatinder Dhaliwal & Kanwaljit Chopra

  2. All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Aagamjit Singh

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  1. Navneet Dhaliwal
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  2. Jatinder Dhaliwal
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  3. Aagamjit Singh
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  4. Kanwaljit Chopra
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Contributions

KC, ND, and JD conceived and designed the experiment. ND and JD conducted the experiments and analyzed the data. ND and AS wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Kanwaljit Chopra.

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Dhaliwal, N., Dhaliwal, J., Singh, A. et al. Dimethyl fumarate attenuates 2-VO-induced vascular dementia via activating the Nrf2 signaling pathway in rats. Inflammopharmacol 29, 537–547 (2021). https://doi.org/10.1007/s10787-020-00785-5

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