Therapeutic Effects of Dimethyl Fumarate on the Rat Model of Brain Ischemia

Owjfard, Maryam; Bigdeli, Mohammad Reza; Safari, Anahid; Namavar, Mohammad Reza

doi:10.1590/s2175-97902022e19677

Cited by 7 publications

(11 citation statements)

References 34 publications

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Section: Anti-inflammationmentioning

confidence: 99%

“…DMF also decreases the expression of apoptotic genes like Bax and Caspase-3 while increasing Bcl-2 expression, which plays a major role in apoptosis regulation (Singh et al, 2019). In a rat model of middle cerebral artery occlusion (MCAO), DMF-treated groups showed an enhanced total number of neurons and a lower number of dead neurons in the right cortical brain (Owjfard et al, 2022).…”

Section: Anti-apoptosis and Cell Survivalmentioning

confidence: 99%

Section: Reducing Cerebral Edemamentioning

confidence: 99%

“…Cytokines and ROS disrupt the BBB and its permeability, leading to circulating neutrophil, monocyte, and lymphocyte infiltration and worsening the inflammation in the ischemic area (Benakis et al, 2015). That being said, animal studies have shown that DMF is capable of affecting BBB permeability and significantly reducing BBB leakage (Owjfard et al, 2022). Ischemic injury releases the chemokine MMP‐9 which degrades the extracellular matrix and increases BBB permeability and facilitates the infiltration of immune cells (Chaturvedi & Kaczmarek, 2014; Lakhan et al, 2009).…”

Section: Role Of Dmf In Ischemic Strokementioning

confidence: 99%

“…A study on rat models demonstrated that DMF minimizes brain water content and cerebral edema formation. This protection is mainly due to increased Nrf2 activity, which leads to the prevention of BBB disruption (Kunze et al, 2015; Owjfard et al, 2022). DMF also reduces edema risk by decreasing the plasma membrane channels responsible for water hemostasis called Aquaporin (AQP)‐4, which are overexpressed during stroke (Liu, Vollmer, et al, 2019).…”

Section: Role Of Dmf In Ischemic Strokementioning

confidence: 99%

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Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke

Owjfard

Karimi²,

Mallahzadeh

et al. 2023

J of Neuroscience Research

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Dimethyl fumarate (DMF) is an immunomodulatory drug currently approved for the treatment of multiple sclerosis and psoriasis. Its benefits on ischemic stroke outcomes have recently come to attention. To date, only tissue plasminogen activators (tPAs) and clot retrieval methods have been approved by the FDA for the treatment of ischemic stroke. Ischemic conditions lead to inflammation through diverse mechanisms, and recanalization can worsen the state. DMF and the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway it regulates seem to be important in postischemic inflammation, and animal studies have demonstrated that the drug improves overall stroke outcomes. Although the exact mechanism is still unknown, studies indicate that these beneficial impacts are due to the modulation of immune responses, bloodbrain barrier permeability, and hemodynamic adjustments. One major component evaluated before, during, and after tPA therapy in stroke patients is blood pressure (BP). Recent studies have found that DMF may impact BP. Both hypotension and hypertension need correction before treatment, which may delay the appropriate intervention. Since BP management is crucial in managing stroke patients, it is important to consider DMF's role in this matter. That being said, it seems further investigations on DMF may lead to an alternative approach for stroke patients. In this article, we discuss the mechanistic roles of DMF and its potential role in stroke based on previously published literature and laboratory findings.

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Section: Anti-inflammationmentioning

confidence: 99%

Section: Anti-apoptosis and Cell Survivalmentioning

confidence: 99%

Section: Reducing Cerebral Edemamentioning

confidence: 99%

Section: Role Of Dmf In Ischemic Strokementioning

confidence: 99%

Section: Role Of Dmf In Ischemic Strokementioning

confidence: 99%

See 3 more Smart Citations

Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke

Owjfard

Karimi²,

Mallahzadeh

et al. 2023

J of Neuroscience Research

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Effect of berberine on the hippocampal structure, biochemical factors, memory, and blood–brain barrier in rat model of transient global cerebral ischemia

Mehboodi,

Shahedi,

Namavar

et al. 2024

Phytotherapy Research

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Global cerebral ischemia (GCI) results in damage to the neurons and leads to cognitive impairments. Berberine (BBR) is known for its neuroprotective qualities. This study aimed to investigate the effects of BBR on memory, Blood–brain barrier (BBB) permeability, biochemical factors, and neuronal structure. Sixty‐three adult male Wistar rats were divided randomly into Sham (21), GCI (21), and GCI + BBR (21) groups. The GCI + BBR group received 50 mg/kg of BBR for 7 days before and 6 h after 20 min of GCI induction. After 24 h, assessments included hippocampal neuronal structure, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPX) levels, memory performance, and BBB permeability. The GCI + BBR group reduced volume loss in the CA1 and its sublayers (oriens, pyramidal, and radiatum) compared to the GCI group (p < 0.0001, p < 0.001, p < 0.01 and p < 0.001, respectively). Additionally, the GCI + BBR group showed higher pyramidal neuron density (p < 0.0001) and number (p < 0.0001) compared to the GCI group. BBR also decreased MDA levels (p < 0.0001) and increased CAT activity (p < 0.0001) in the GCI + BBR group compared to the GCI group, with GPX and SOD activity approaching Sham levels (p < 0.0001, both). BBR demonstrated significant improvements in short and long‐term memory compared to the GCI group (p < 0.01, p < 0.0001, respectively). Furthermore, BBB permeability in the GCI + BBR group was significantly reduced compared to the GCI group (p < 0.0001). These findings demonstrated BBR's potential to protect the neurons in the CA1 and BBB structures, enhance antioxidant activity, and alleviate GCI‐induced memory impairments.

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Therapeutic Effects of Intranasal Administration of Resveratrol on the Rat Model of Brain Ischemia

Owjfard,

Rahimian,

Ghaderpanah

et al. 2024

Heliyon

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Therapeutic Effects of Dimethyl Fumarate on the Rat Model of Brain Ischemia

Cited by 7 publications

References 34 publications

Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke

Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke

Effect of berberine on the hippocampal structure, biochemical factors, memory, and blood–brain barrier in rat model of transient global cerebral ischemia

Therapeutic Effects of Intranasal Administration of Resveratrol on the Rat Model of Brain Ischemia

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