1. Possible Neuroprotective Effects of Magnesium Sulfate and Melatonin as Both Pre- and Post-Treatment in a Neonatal Hypoxic-Ischemic Rat Model
- Author
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Tulin Alkan, Merih Cetinkaya, Nilgün Köksal, Ilker Mustafa Kafa, Mustafa Ayberk Kurt, Fadil Ozyener, Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Saǧlıǧı ve Hastalıkları Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Psikoloji Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı., Çetinkaya, Merih, Alkan, Tülin, Özyener, Fadil, Kafa, İlker Mustafa, Kurt, Mustafa Ayberk, Köksal, Nilgün, AAH-1792-2021, AAG-7125-2021, AAH-1641-2021, AAG-8393-2021, and AAR-4341-2020
- Subjects
genetic structures ,Drug Evaluation, Preclinical ,Apoptosis ,Hippocampal CA3 region ,Pharmacology ,Pediatrics ,Hypoxia ischemia ,Animal tissue ,Rats, Sprague-Dawley ,Hippocampal CA1 region ,Pregnancy ,Brain-injury ,Hypoxia-ischemia ,Pre and post ,Priority journal ,Melatonin ,Conference paper ,Magnesium ,Neuroprotection ,Drug Combinations ,Damage ,Neuroprotective Agents ,Randomized controlled trial ,Anesthesia ,Hypoxia-Ischemia, Brain ,Newborn rats ,Female ,Protects ,Infants ,Hypoxic ischemic encephalopathy ,Pretreatment ,Eclampsia ,Magnesium Sulfate ,Pregnancy Toxemia ,Algorithms ,medicine.drug ,Sodium chloride ,Rat model ,chemistry.chemical_element ,Drug Administration Schedule ,Brain ischemia ,medicine ,Brain infarction size ,Animals ,Animal model ,Dentate gyrus ,Animal experiment ,Brain hypoxia ,Infusion ,Consequences ,Hypoxic ischemic ,Rattus ,business.industry ,Birth asphyxia ,Adrenal cortex ,Nonhuman ,Rats ,Disease Models, Animal ,Animals, Newborn ,chemistry ,Pediatrics, Perinatology and Child Health ,Rat ,Cell-death ,business ,Controlled study ,Developmental Biology - Abstract
Background: Perinatal hypoxia-ischemia is a major cause of mortality and long-term neurological deficits. Objectives: The objective of this study was to compare the effects of two neuroprotective agents; magnesium sulfate and melatonin, administered alone or in combination, on brain infarct volume and TUNEL positivity in a neonatal hypoxic-ischemic (HI) rat model. Methods: After being anesthetized, 7-day-old pups (n = 80) underwent ischemia followed by exposure to hypoxia for 2 h. The pups were then divided equally and randomly into 4 groups in order to receive the vehicle (saline, control group), magnesium sulfate, melatonin or a combination of magnesium sulfate and melatonin. Treatments were administered intraperitoneally three times; the first being just before ischemia, the second after hypoxia and the third 24 h after the second dose. The pups were sacrificed on postnatal day 10, their brains harvested and evaluated for infarct volume and neuronal apoptosis. Results: Percent infarcted brain volume was significantly reduced in pups receiving the drugs (either magnesium sulfate, melatonin or their combination) compared with those receiving the vehicle. In addition, TUNEL staining showed markedly reduced numbers of TUNEL-positive cells per unit area in the CA1, CA3 and dentate gyrus regions of the hippocampus and in the cortex. However, no statistically significant differences were found regarding percent infarcted brain volume and number of TUNEL-positive cells among the drug-treated groups. Conclusions: Magnesium sulfate and melatonin, two agents acting at different stages of HI brain damage, administered either alone or in combination, significantly reduced the percent infarcted brain volume and TUNEL positivity, suggesting that these agents may confer a possible benefit in the treatment of infants with HI encephalopathy.
- Published
- 2010
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