Neuroprotective effect of ethanol and Modafinil on focal cerebral ischemia in rats

Shabani, Ronak; Mousavizadeh, Kazem; Soleimani, Mansoureh; Abbasi, Yusef

doi:10.1007/s11011-018-0378-0

Cited by 18 publications

(13 citation statements)

References 59 publications

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“…Our results indicated that both single and combination therapy of modafinil (in a dose-dependent manner) and ethanol increased the anxiety but improved neurological function and locomotor activity in ischemia-induced rats. Our previous study showed that both single and combination therapy of modafinil (in a dose-dependent manner) and ethanol decreased apoptosis and increased neuroprotective effect after focal cerebral ischemia (Abbasi, Shabani, Mousavizadeh, Soleimani, & Mehdizadeh, 2019). Light-to-moderate alcohol consumption decreases the mortality and infarct volume after cerebral ischemia (McCarter et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Behavioral Changes in Combination Therapy of Ethanol and Modafinil on rats Focal Cerebral Ischemia

Abbasi

Mousavizadeh

Shabani

et al. 2020

Basic Clin. Neurosci. J.

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Ethanol is considered as an effective agent in reducing brain stroke injury. In this study, we assessed the effects of modafinil along with ethanol as a combination therapy on behavioral function in Wistar rats. Methods: The right Middle Cerebral Artery Occlusion (MCAO) was performed and the rats were divided into nine groups (n=8 per group). The animal groups in this study were as follows: 1. MCAO control group (ischemia without treatment); 2. Vehicle group; 3. Modafinil group that was randomly subdivided into three groups receiving different doses of modafinil (10, 30, and 100 mg/kg) for 7 days before MCAO; 4. Ethanol group receiving 1.5 g/kg ethanol at the time of reperfusion; 5. Modafinil + ethanol group that was further subdivided into three groups receiving modafinil at different doses (10, 30, and 100 mg/kg) for 7 days before MCAO and ethanol at the time of reperfusion. The motor behavior was measured using the Garcia test 24, 48, and 72 h after the ischemia, and the elevated body swing test was performed 48 and 72 h after the ischemia. The anxiety and locomotor activity were analyzed by open field test 48 and 72 h post-ischemia. Results: The results showed that the neurological deficit score, locomotor activity, and unexpected thigmotaxis (anxiety) in the ethanol, modafinil (in a dose-dependent manner), and ethanol+modafinil treatment groups were significantly higher than the MCAO control group. Conclusion: It seems that the combination therapy of modafinil (100 mg/kg) and ethanol (1.5 g/kg) significantly enhanced neuroprotection via an improvement in locomotor activity and neurological functions.

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Section: Discussionmentioning

confidence: 99%

Behavioral Changes in Combination Therapy of Ethanol and Modafinil on rats Focal Cerebral Ischemia

Abbasi

Mousavizadeh

Shabani

et al. 2020

Basic Clin. Neurosci. J.

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“…In AIS, various ameliorative therapies were observed to confer bene t while inhibiting hyperglycolysis. Ethanol and moda nil, each of which are known to be neuroprotective, in combination inhibited hyperglycolysis in attenuating AIS damage [24]. Normobaric O 2 [25] and ischemic preconditioning [60] modulated signaling pathways to subdue hyperglycolysis in postischemic states.…”

Section: Discussionmentioning

confidence: 99%

“…Speci cally in AIS, hyperglycolysis contributes to the energy crisis that ultimately leads to brain damage [23]. More convincingly, many treatment modalities have ameliorated AIS damage by decreasing hyperglycolysis [24,25], one of which includes C+P [26].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Pharmacological Hypothermia on Glucose Metabolism in Ischemic Rats

Guan

Lee

et al. 2021

Preprint

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Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential neuroprotective strategy for stroke in which the temperature can be decreased safely. The present study determined whether neuroprotective PH with chlorpromazine and promethazine (C+P) plus dihydrocapsaicin (DHC) improved glucose metabolism in acute ischemic stroke. A total of 208 adult male Sprague-Dawley rats were randomly divided into the following groups: sham, stroke, and stroke with various treatments including C+P, DHC, C+P+DHC, phloretin (glucose transporter (GLUT)-1 inhibitor), cytochalasin B (GLUT-3 inhibitor), TZD (thiazolidinedione, phosphoenolpyruvate carboxykinase (PCK) inhibitor) and apocynin (nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor). Stroke was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 6 or 24 h of reperfusion. Rectal temperature was monitored before, during, and after PH. Infarct volume and neurological deficits were measured to assess the neuroprotective effects. Reactive oxygen species (ROS), NOX activity, lactate, apoptotic cell death, glucose, and ATP levels were measured. Protein expressions of GLUT-1, GLUT-3, phosphofructokinase (PFK), lactate dehydrogenase (LDH), PCK1, PCK2, and NOX subunit gp91 were measured with Western blotting. PH with combination of C+P and DHC induced a faster, longer, and deeper hypothermia as compared to each alone. PH significantly improved every measured outcome as compared to stroke and monotherapy. PH reduced brain infarction, neurological deficits, protein levels of glycolytic enzymes (GLUT-1, GLUT-3, PFK and LDH), gluconeogenic enzymes (PCK1 and PCK2), NOX activity and its subunit gp91, ROS, apoptotic cell death, glucose, and lactate, while raising ATP levels. In conclusion, stroke impaired glucose metabolism by enhancing hyperglycolysis and gluconeogenesis, which led to ischemic injury, all of which were reversed by PH induced by a combination of C+P and DHC.

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“…The results also revealed that Caspase‐3 and Caspase‐8 levels were significantly elevated in the ischemic stroke group compared to the untreated group. Modafinil has high antioxidant and anti‐inflammatory properties (Fong, 2018b) that can increase the antioxidant capacity of brain cells (Abbasi, Shabani, Mousavizadeh, Soleimani, & Mehdizadeh, 2019). Increased antioxidant capacity prevents Reactive oxygen species formation (Kovacic & Weston, 2017).…”

Section: Discussionmentioning

confidence: 99%

Modafinil‐coated nanoparticle increases expressions of brain‐derived neurotrophic factor, glial cell line‐derived neurotrophic factor and neuronal nuclear protein, and protects against middle cerebral artery occlusion‐induced neuron apoptosis in the rat hippocampus

Torfeh

Abdolmaleki

Nazarian

et al. 2020

The Anatomical Record

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The present study investigates the neuroprotective effects of modafinil‐coated nanoparticle in rats' hippocampal CA1 region. Male Wistar rats (n = 48) were randomly divided into four groups. Then middle cerebral artery occlusion (MCAO) was performed by inserting a silicone coat filament in the right internal carotid artery via the external carotid artery until it reached the anterior cerebral artery. Modafinil (100 mg/kg) or modafinil‐coated nanoparticle (100 mg/kg) was given to the rats as an oral gavage once a day. Infarct volume, brain‐derived neurotrophic factor (BDNF), glial cell line‐derived neurotrophic factor (GDNF), neuronal nuclear protein (NeuN) and Caspase‐3 and, Caspase‐8 as apoptotic genes were measured in the hippocampal CA1 region. Cresyl violet staining revealed that modafinil nanoparticle significantly decreased the neurodegeneration. Reverse transcription polymerase chain reaction results showed that modafinil nanoparticle use significantly increased the expression of neurotrophic factors (even more than modafinil alone group; p = .01). Moreover, the apoptotic markers were significantly decreased in nanoparticle modafinil (MN group); p < .05). The western blot analysis and Immunohistochemistry results confirmed the neuroprotective and anti‐apoptotic effects of modafinil nanoparticle. This study's results showed that the use of modafinil‐coated nanoparticle has neuroprotective effects by increasing neurotrophic factors and reducing apoptosis after MCAO in the CA1 area of the hippocampus. However, further studies are needed especially, in human samples.

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Neuroprotective effect of ethanol and Modafinil on focal cerebral ischemia in rats

Cited by 18 publications

References 59 publications

Behavioral Changes in Combination Therapy of Ethanol and Modafinil on rats Focal Cerebral Ischemia

Behavioral Changes in Combination Therapy of Ethanol and Modafinil on rats Focal Cerebral Ischemia

Neuroprotective Effects of Pharmacological Hypothermia on Glucose Metabolism in Ischemic Rats

Modafinil‐coated nanoparticle increases expressions of brain‐derived neurotrophic factor, glial cell line‐derived neurotrophic factor and neuronal nuclear protein, and protects against middle cerebral artery occlusion‐induced neuron apoptosis in the rat hippocampus

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