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

  • Yusef Abbasi
  • Ronak Shabani
  • Kazem Mousavizadeh
  • Mansoureh Soleimani
  • Mehdi MehdizadehEmail author
Original Article
  • 35 Downloads

Abstract

Ethanol is known as an effective agent against cerebral lesions after ischemia. Modafinil is a stimulant of the central nervous system (CNS) with antioxidant properties. We assessed the neuroprotective effect of modafinil in combination with ethanol after focal cerebral ischemia. Male wistar rats weighing 280–300 g were divided into nine groups (n = 12 each group): The groups consisted of the MCAO (middle cerebral artery occlusion) group (i.e. ischemia without treatment); the vehicle group(Dimethylsulfoxide); the modafinil group including three subgroups which pretreated with Modafinil (10, 30, 100 mg/kg), respectively, for seven days prior to the induction of MCAO; the ethanol group which received 1.5g/kg ethanol at the time of reperfusion; and modafinil+ethanol group which was divided into three subgroups that received three doses of modanifil (10, 30,100 mg/kg), respectively, for seven days prior to MCAO as well as ethanol at the time of reperfusion. Transient cerebral ischemia was induced by 60-min intraluminal occlusion of the right middle cerebral artery. Edema, infarct volume, glial scar formation (gliosis) and apoptosis were analyzed. The ethanol alone treatment (with a less significant effect), modafinil (in a dose-dependent way), and the combination of modafinil and ethanol significantly decreased the brain infarct volume, edema, apoptosis, and gliosis (P ≤ 0.05). Additionally, modafinil+ethanol mediated the restoration of aerobic metabolism and hyper-glycolysis suppress, thereby resulting in an increase in pyruvate dehydrogenase and a decrease in lactate dehydrogenase activity, respectively, which ultimately reduced oxidative reperfusion injury. These results demonstrate that pretreatment with modafinil (100 mg/kg) and modafinil+ethanol(1.5 g/kg) may prevent ischemic brain injuries.

Keywords

Neuroprotection Ethanol Modafinil Cerebral ischemia Rat 

Notes

Acknowledgements

This study was financially supported by a research grant from Iran University of Medical Sciences. Our thanks go to Sobhan Darou Pharmaceutical Company for providing us with the pure form of modafinil.

Funding

This study was financially supported by a research grant from Iran University of Medical Science (grant number:29298) for a Ph.D. student thesis.

Compliance with ethical standards

Conflicts of interests

Conflict of interest the authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of ethics Committee of Iran University of Medical Sciences (ethical code: ir.iums.rec 1395.9221313204).

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Authors and Affiliations

  1. 1.Department of Anatomy, Faculty of MedicineIran University of Medical SciencesTehranIran
  2. 2.Cellular and Molecular Research Center, Faculty of MedicineIran University of Medical SciencesTehranIran
  3. 3.Department of Molecular Medicine, Faculty of Advanced Technologies in MedicineIran University of Medical SciencesTehranIran

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