Neonatal Med.  2014 May;21(2):129-137. 10.5385/nm.2014.21.2.129.

The Effect of Combination Treatment of Melatonin and Hypothermia on Hypoxic-Ischemic Brain Injury in Neonatal Rats

Affiliations
  • 1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 2Department of Pediatrics, Keimyung University School of Medicine, Daegu, Korea. cskim@dsmc.or.kr
  • 3Department of Pharmacology, Keimyung University School of Medicine, Daegu, Korea.

Abstract

PURPOSE
Melatonin is a naturally occurring hormone produced by the pineal gland. Melatonin has many pharmacological effects in different tissues or organs. Melatonin is especially known to have antioxidant and neuroprotective effects. Hypothermia is a therapeutic tool against hypoxia-ischemia (HI) of the brain. This study examines the effect of combined therapy using melatonin and hypothermia in neonatal rats with HI.
METHODS
Seven-day old rats were subjected to HI and randomized into four groups : vehicle, melatonin alone, vehicle and hypothermia, and melatonin and hypothermia. Melatonin (30 mg/kg) was intraperitoneally administered in two doses: immediately following HI, and 24 h later. Hypothermia consisted of whole-body cooling (3 hours, 27degrees C). Sham-treated animals not subjected to HI were also studied. P10, P14, and P35 rats were sacrificed for experiments.
RESULTS
Vehicle-treated P10 rats increased in brain infarction compared to controls in TTC staining study. And also, P35 rats decreased in brain volume of injured hemisphere in H&E stain. Melatonin or hypothermia alone did not show any protective effect against HI. However, a combination of melatonin and hypothermia effectively reduced the brain injury. In addition, the results of in situ zymography, TUNEL assay and immunofluorescence studies showed that neuroprotective effects were achieved only with combined therapy.
CONCLUSION
Melatonin may contribute to synergistic effects to neuroprotection of hypothermia on brain damage after HI.

Keyword

Melatonin; Hypothermia; Hypoxia-ischemia

MeSH Terms

Animals
Brain
Brain Infarction
Brain Injuries*
Fluorescent Antibody Technique
Hypothermia*
In Situ Nick-End Labeling
Melatonin*
Neuroprotective Agents
Pineal Gland
Rats*
Melatonin
Neuroprotective Agents
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