Title:Dimethyl Fumarate Attenuates Behavioral and Structural Impairments
Associated with Brain Ischemia in Rats
Volume: 26
Issue: 1
Author(s): Mohammad Bakhtiari, Masoumeh Emamghoreishi, Maryam Khastkhodaei Ardakani and Mohammad Reza Namavar*
Affiliation:
- Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Clinical
Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Keywords:
Ischemic stroke, dimethyl fumarate, edaravone, stereology.
Abstract:
Introduction: Ischemic stroke remains one of the leading causes of death and physical
and mental disability. Oxidative stress, free radicals, and inflammation play critical roles in ischemic brain damage. Free radical scavengers such as edaravone and dimethyl fumarate (DMF),
known for their antioxidant and anti-inflammatory properties, are considered promising targets for
ischemic stroke treatment. This study aimed to assess the impact of these drugs on brain ischemia.
Methods: Forty-nine rats were randomly divided into seven groups: sham, edaravone, and DMF
controls, as well as edaravone, DMF 5, 15, and 30 groups. Middle cerebral artery occlusion
(MCAO) was induced in all groups except the sham group. The MCAO groups were administered
with either the vehicle, edaravone (3 mg/kg), or DMF at doses of 5, 15, and 30 mg/kg twice daily
for 14 days. Neurobehavioral assessments were conducted throughout the experiment, and anatomical changes in the brain were evaluated using stereological methods.
Results: Edaravone and three doses of DMF improved neurobehavioral functions. All treated rats
showed a reduction in the ischemic volume and cell loss in the brain regions when compared with
the control animals. MCAO reduced the total number of neurons and just DMF doses had a significant effect on this factor. Interestingly, MCAO increased the number of non-neurons and only the
DMF 30 group significantly decreased this parameter. DMF 30 was more effective in ischemic
stroke.
Conclusions: Although edaravone improved neurological functions and reduced the size of brain
ischemia and cell loss, DMF, especially at higher doses, exerted a more beneficial effect on these
parameters. Therefore, DMF could be proposed as a reinforcement to currently conventional therapies
