Published online August 25, 2008
PEDIATRICS Vol. 122 No. 3 September 2008, pp. e722-e727 (doi:10.1542/peds.2008-0269)
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ARTICLE

Free Radical Injury and Blood-Brain Barrier Permeability in Hypoxic-Ischemic Encephalopathy

Ashok Kumar, MDa, Roopali Mittal, MDb, Hari Dev Khanna, MDc and Sriparna Basu, MDa

a Division of Neonatology
b Department of Pediatrics
c Department of Biophysics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

OBJECTIVES. The purpose of this work was to evaluate the extent of free radical injury in newborns with hypoxic ischemic encephalopathy by measuring plasma levels of malondialdehyde and nitric oxide and to assess the blood-brain barrier permeability by measuring the cerebrospinal fluid albumin/plasma albumin ratio.

METHODS. This prospective observational study was conducted over a period of 2 years at Sir Sundarlal Hospital, Banaras Hindu University. The study population consisted of 43 term neonates with perinatal asphyxia who subsequently developed hypoxic ischemic encephalopathy. Twenty normal gestational age- and gender-matched healthy infants without any perinatal asphyxia served as control subjects. Peripheral venous blood samples were analyzed for malondialdehyde, total plasma nitrates/nitrites, and albumin levels between 12 and 24 hours of life. To assess the blood-brain barrier permeability, the cerebrospinal fluid albumin/plasma albumin ratio was measured. Correlation among the levels of malondialdehyde, nitrates/nitrites, and blood-brain barrier permeability was calculated. Data were analyzed by using SPSS 10 software.

RESULTS. Plasma malondialdehyde and nitrate/nitrite levels were significantly higher in infants with hypoxic ischemic encephalopathy compared with control subjects. Although there was a progressive increment in plasma levels of malondialdehyde with increasing severity of hypoxic ischemic encephalopathy, the differences were not statistically significant. Plasma nitrate/nitrite levels were almost similar in all stages of hypoxic ischemic encephalopathy. Plasma albumin levels were comparable in infants with hypoxic ischemic encephalopathy and control subjects, whereas cerebrospinal fluid albumin levels and blood-brain barrier permeability were significantly higher in infants with hypoxic ischemic encephalopathy. Significant correlation was observed between plasma malondialdehyde and nitrate/nitrite levels with blood-brain barrier permeability.

CONCLUSIONS. Increased plasma levels of malondialdehyde and nitrates/nitrites are found to be associated with hypoxic ischemic encephalopathy, indicating the possible role of free radical injury in its causation. Increased blood-brain barrier permeability may be another contributory factor to the progression of the disease.

Key Words: blood-brain barrier permeability • hypoxic ischemic encephalopathy • lipid peroxidation • malondialdehyde • newborn • nitric oxide • perinatal asphyxia

Abbreviations: HIE—hypoxic ischemic encephalopathy • NO—nitric oxide • BBB—blood-brain barrier • CSF—cerebrospinal fluid • SNK—Student-Newman-Keuls • NOS—nitric-oxide synthase • nNOS—neuronal nitric-oxide synthase • eNOS—endothelial nitric-oxide synthase • iNOS—inducible nitric-oxide synthase • VEGF—vascular endothelial growth factor

Accepted Apr 29, 2008.


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