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

Dhaliwal, Navneet; Dhaliwal, Jatinder; Singh, Aagamjit; Chopra, Kanwaljit

doi:10.1007/s10787-020-00785-5

Cited by 11 publications

(10 citation statements)

References 57 publications

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“… 37 Moreover, no significant difference was observed on locomotor activity in an actophotometer after the 4-week oral DMF treatment with a dose of 15, 30 and 60 mg/kg in Sprague-Dawley rats. 38 In line with these findings, we did not observe locomotor sensitization after the 3-week oral DMF treatment (data not shown), as indicated by the distance swum and velocity in the Morris Water Maze without platform (probe test).…”

Section: Methodssupporting

confidence: 83%

Dimethyl Fumarate as the Peripheral Blood Inflammatory Mediators Inhibitor in Prevention of Streptozotocin-Induced Neuroinflammation in Aged Rats

Wrona¹,

Majkutewicz²,

Gabriela³

et al. 2022

JIR

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Purpose: Intracerebroventricular-(ICV)-streptozotocin-(STZ)-induced neuroinflammation is a model of Alzheimer's disease (AD) compatible with the inflammation hypothesis of ageing ("inflammaging" state). Previously, we observed age-dependent (young vs aged) dimethyl fumarate (DMF)-induced anti-inflammatory and neuroprotective effects in the brain along with improvement in cognitive functions in rats with the ICV-STZ-induced model of AD. To evaluate whether DMF reduces neuroinflammation based on the peripheral inflammatory response inhibition, we determined peripheral inflammatory mediators in young and aged rats with the ICV-STZ-induced AD pathology following DMF therapy. Materials and Methods: Young (4-month-old) and aged (22-month-old) rats were fed with 0.4% DMF rat chow for 21 consecutive days after ICV-STZ (3 mg/ventricle) injections. After behavioral testing, blood and spleens were collected to determine the numbers of leukocytes (WBC), lymphocytes and their subpopulations, haematological parameters, the concanavalin (Con)-A-induced production and plasma concentration of interferon (IFN)-γ, interleukin (IL)-6, IL-10 and corticosterone (COR). Results: Age-dependent anti-inflammatory effect of the DMF treatment in rats with ICV-STZ injections manifested as decreased peripheral WBC and lymphocyte numbers, including TCD3 + CD4 + CD8 − , TCD3 + CD4 − CD8 + , B (CD45RA + ) and NK (161a + ), in aged rats. Furthermore, DMF lowered the blood and spleen lymphocyte production of pro-inflammatory IFN-γ and IL-6 in young and aged rats, whereas it enhanced the plasma level of antiinflammatory IL-10 and lymphocyte's ability to produce it in aged rats only. In parallel to changes in peripheral WBC numbers in the model of AD, DMF decreased the red blood cell number, haemoglobin concentration, haematocrit and mean platelet volume in aged, but not young, rats. In contrast to controls, DMF did not influence the COR response in STZ groups. Conclusion: Besides preventing neuroinflammation, DMF acts on the pro-/antiinflammatory balance in the periphery and causes an anti-inflammatory shift in T lymphocytes which could contribute to DMF's therapeutic effects in the ICV-STZinduced model of AD, in particular, in aged rats.

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Section: Methodssupporting

confidence: 83%

Dimethyl Fumarate as the Peripheral Blood Inflammatory Mediators Inhibitor in Prevention of Streptozotocin-Induced Neuroinflammation in Aged Rats

Wrona¹,

Majkutewicz²,

Gabriela³

et al. 2022

JIR

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“…Due to the loss of limb function following a stroke, many tests focus on motor and sensory testing (Lipsanen et al, 2011;Makkiyah et al, 2021;Sun et al, 2016;Wakayama et al, 2007). Because learning and memory problems are frequent after a stroke, cognitive testing is particularly important for determining the full extent of the difficulties (Barros et al, 2009;Dhaliwal et al, 2021;Hei et al, 2018;Yao et al, 2021). As a result, it's critical to have sensitive behavioural approaches for detecting the wide range of deficits that might arise after a stroke.…”

Section: Discussionmentioning

confidence: 99%

Behaviour test in chronic brain ischemia rats: A bibliometric approach

et al. 2022

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Background: Stroke causes severe disability and mortality. Despite the fact that the pathology of acute stroke is well understood, publication on chronic stroke is still limited. Because scarring of glia limits the recovery area of acute stroke and reorganization capacity is reduced, discovering new treatments for chronic stroke poses substantial obstacles. In stroke research, rodent models are commonly utilized, and behavior testing is a crucial tool. To measure stroke outcomes and translating rodent findings to therapeutic trials, selecting relevant behavioral tests that fit the study purpose is critical. Here, we aimed to look at the last decade’s publications highlighting behaviour tests on chronic stroke rats. Hopefully, we were able to give more information about the behaviour tests to facilitate the researchers’ choice of appropriate test. Methods: By using a bibliometric analysis, we hope to systematically discuss rodent behavior tests in chronic stroke research. Documents were extracted from the Scopus database in April 2022. Excel and VOSviewer 1.6.18 were used to conduct statistical and graphical analysis. Results: Research on "behavioral test in chronic stroke rats" has progressed quickly, although the researchers have yet to collaborate with each other. H. Millani was an active researcher and author who connected numerous researchers, according to documents and citation analysis. “Animals”, “brain ischemia”, “man”, “publication”, and “animal experiment” were all common keywords. The majority of the articles were from the United States and China. The Morris Water Maze test and the cylinder test were the most commonly used behavior tests. Conclusions Clinical applications and therapeutic effectiveness against stroke could be improved with more collaboration amongst authors. When using a behavior test, researchers need to think about which neurological deficiency is being addressed and whether the test covers long-term evaluation.

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“…Sulforaphane, another potent NRF2 activating compound found in cruciferous vegetables, ameliorated cognitive deficits in mouse models of Alzheimer’s disease, traumatic brain injury and vascular cognitive impairment [ 51 , 52 , 53 , 54 ]. Cognitive enhancing effects of DMF have also been described in rodent models of sepsis and vascular dementia [ 55 , 56 ]. Even more convincing perhaps is a recent finding from a clinical trial of DMF in multiple sclerosis patients showing slowed cognitive decline over two years of treatment [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

NRF2 Activation Ameliorates Oxidative Stress and Improves Mitochondrial Function and Synaptic Plasticity, and in A53T α-Synuclein Hippocampal Neurons

et al. 2021

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In Parkinson’s disease (PD), brain oxidative stress and mitochondrial dysfunction contribute to neuronal loss as well as motor and cognitive deficits. The transcription factor NRF2 has emerged as a promising therapeutic target in PD because it sits at the intersection of antioxidant and mitochondrial pathways. Here, we investigate the effects of modulating NRF2 activity in neurons isolated from a A53T α-synuclein (A53TSyn) mouse model of synucleinopathy. Embryonic hippocampal neurons were isolated from A53TSyn mice and their wild type (WT) littermates. Neurons were treated with either the NRF2 activator dimethyl fumarate (DMF) or the NRF2 inhibitor ML385. Reactive oxygen species (ROS), dendritic arborization and dendritic spine density were quantified. Mitochondrial bioenergetics were also profiled in these neurons. A53TSyn neurons had increased ROS and reduced basal and maximal mitochondrial respiration relative to WT neurons. A53TSyn neurons also displayed decreased dendritic arborization and reduced spine density. Treatment with DMF reduced ROS levels and improved both mitochondrial function and arborization, while inhibition of NRF2 with ML385 exacerbated these endpoints. Modulation of NRF2 activity had a significant effect on mitochondrial function, oxidative stress, and synaptic plasticity in A53TSyn neurons. These data suggest that NRF2 may be a viable target for therapeutic interventions in PD.

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

Cited by 11 publications

References 57 publications

Dimethyl Fumarate as the Peripheral Blood Inflammatory Mediators Inhibitor in Prevention of Streptozotocin-Induced Neuroinflammation in Aged Rats

Dimethyl Fumarate as the Peripheral Blood Inflammatory Mediators Inhibitor in Prevention of Streptozotocin-Induced Neuroinflammation in Aged Rats

Behaviour test in chronic brain ischemia rats: A bibliometric approach

NRF2 Activation Ameliorates Oxidative Stress and Improves Mitochondrial Function and Synaptic Plasticity, and in A53T α-Synuclein Hippocampal Neurons

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