| نویسندگان | فيروزي پريسا , الهام قاسملو ,forouzandeh Meysam ,Eskandari Mehdi ,Ganjkhani Mahin ,Hosseini Massomeh ,Majdi Ali ,Perdeh Bahram ,Rostami Ali ,Mostafavi Hossein |
|---|---|
| نشریه | NEUROLOGICAL RESEARCH |
| شماره صفحات | ۱ |
| صفحه پايان | 13 |
| نوع مقاله | Full Paper |
| تاریخ انتشار | ۱۴۰۵ |
| رتبه نشریه | معتبر بینالمللی (WOS/Scopus) Q2 |
| نوع نشریه | الکترونیکی |
| کشور محل چاپ | ایرلند |
چکیده مقاله
ABSTRACT
Background: Ischemic stroke is a major cause of mortality and disability worldwide, with
limited effective neuroprotective treatments. Epigenetic modulation and oxidative stress
regulation have emerged as promising therapeutic targets. This study aimed to evaluate
the neuroprotective effects of melatonin and valproic acid, alone and in combination, in
a rat model of cerebral ischemia.
Methods: Male Wistar rats were randomly divided into nine groups including sham,
MCAO, vehicle, melatonin, valproic acid, and different combination treatment groups.
Cerebral ischemia was induced using the middle cerebral artery occlusion (MCAO)
method. Neurological deficits, infarct volume, brain edema, antioxidant activity, and
gene expression of HDAC1, HDAC3, MT1, and MT2 were evaluated.
Results: Both melatonin and valproic acid significantly improved neurological out
comes, reduced infarct volume, and decreased brain edema compared to the MCAO
group. Combination therapy, particularly at high doses, showed significantly greater
neuroprotective effects than monotherapy. These effects were associated with down
regulation of HDAC1 and HDAC3 expression, upregulation of MT1 and MT2 receptors,
and increased antioxidant enzyme activity including catalase and superoxide dismutase
levels.
Conclusion: Combined administration of melatonin and valproic acid exerts synergistic
neuroprotective effects in cerebral ischemia through modulation of oxidative stress,
epigenetic regulation, and melatonin receptor signaling. This combination may repre
sent a promising therapeutic strategy for ischemic stroke.
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