Possible neuroprotective effects of magnesium sulfate and melatonin as both pre- and post-treatment in a neonatal hypoxic-ischemic rat model.
BACKGROUND
Perinatal hypoxia-ischemia is a major cause of mortality and long-term neurological deficits.


OBJECTIVE
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.
Department of Pediatrics, Division of Neonatology, Faculty of Medicine, Uludag University, Bursa, Turkey. drmerih@yahoo.com
Merih
M
Cetinkaya
Tülin
T
Alkan
Fadil
F
Ozyener
Ilker Mustafa
IM
Kafa
Mustafa Ayberk
MA
Kurt
Nilgun
N
Koksal
D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology; D008278:Magnesium Sulfate / Q000008:administration & dosage* / Q000494:pharmacology*; D008550:Melatonin / Q000008:administration & dosage* / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004338:Drug Combinations; D018696:Neuroprotective Agents; D008278:Magnesium Sulfate; D008550:Melatonin