New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury. 2011

Brankica Vasiljevic, and Svjetlana Maglajlic-Djukic, and Miroslava Gojnic, and Sanja Stankovic, and Svetlana Ignjatovic, and Dragana Lutovac
Department of Neonatology, Institute of Gynecology and Obstetrics - Clinical Centre of Serbia, Belgrade, Serbia. bdvasilj@eunet.rs

BACKGROUND Pathogenesis of perinatal hypoxic-ischemic brain injury (HIE) is complex. In this study, we examined the role of neuroinflammation, oxidative stress and growth factors in perinatal hypoxic-ischemic brain damage. METHODS Ninety neonates (>32 weeks' gestation) with perinatal HIE were enrolled prospectively. Perinatal HIE was categorized into three stages according to the Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated electroencephalography. Cerebrospinal fluid (CSF) for interleukin-6 (IL-6) and glutathione peroxidase analysis was taken in the first 48 h of life and subsequent CSF for neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF) analysis 72 h after birth. Neurodevelopmental outcome was assessed at 12 months of corrected gestational age using the Denver Developmental Screening Test. RESULTS Concentrations of NSE in CSF correlated with severity of HIE (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Concentrations of IL-6 in CSF were markedly increased in neonates with severe HIE (P < 0.0001) and those with subsequent neurological sequels, but were normal in the majority of neonates with mild and moderate HIE. Glutathione peroxidase activity in CSF was significant with the stage of HIE (P < 0.0001) and gestational age (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Advanced stage of HIE was associated with increased concentrations of VEGF in CSF (P < 0.0001). Neurological outcomes at 12 months of age correlated best with CSF level of NSE (P < 0.001) and IL-6 (P < 0.001). CONCLUSIONS Our results suggest that neuroinflammation plays a principal role in perinatal hypoxic-ischemic brain damage and we postulate that oxidative stress and upregulation of VEGF might be important contributing factors in the pathogenesis of hypoxic-ischemic brain injury, particularly in preterm neonates.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008297 Male Males
D010751 Phosphopyruvate Hydratase A hydro-lyase that catalyzes the dehydration of 2-phosphoglycerate to form PHOSPHOENOLPYRUVATE. Several different isoforms of this enzyme exist, each with its own tissue specificity. Enolase,Neuron-Specific Enolase,2-Phospho-D-Glycerate Hydro-Lyase,2-Phospho-D-Glycerate Hydrolase,2-Phosphoglycerate Dehydratase,Enolase 2,Enolase 3,Muscle-Specific Enolase,Nervous System-Specific Enolase,Non-Neuronal Enolase,alpha-Enolase,beta-Enolase,gamma-Enolase,2 Phospho D Glycerate Hydro Lyase,2 Phospho D Glycerate Hydrolase,2 Phosphoglycerate Dehydratase,Dehydratase, 2-Phosphoglycerate,Enolase, Muscle-Specific,Enolase, Nervous System-Specific,Enolase, Neuron-Specific,Enolase, Non-Neuronal,Hydratase, Phosphopyruvate,Hydro-Lyase, 2-Phospho-D-Glycerate,Muscle Specific Enolase,Nervous System Specific Enolase,Neuron Specific Enolase,Non Neuronal Enolase,System-Specific Enolase, Nervous,alpha Enolase,beta Enolase,gamma Enolase
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D002547 Cerebral Palsy A heterogeneous group of nonprogressive motor disorders caused by chronic brain injuries that originate in the prenatal period, perinatal period, or first few years of life. The four major subtypes are spastic, athetoid, ataxic, and mixed cerebral palsy, with spastic forms being the most common. The motor disorder may range from difficulties with fine motor control to severe spasticity (see MUSCLE SPASTICITY) in all limbs. Spastic diplegia (Little disease) is the most common subtype, and is characterized by spasticity that is more prominent in the legs than in the arms. Pathologically, this condition may be associated with LEUKOMALACIA, PERIVENTRICULAR. (From Dev Med Child Neurol 1998 Aug;40(8):520-7) Diplegic Infantile Cerebral Palsy,Little Disease,Monoplegic Cerebral Palsy,Quadriplegic Infantile Cerebral Palsy,Spastic Diplegia,CP (Cerebral Palsy),Cerebral Palsy, Athetoid,Cerebral Palsy, Atonic,Cerebral Palsy, Congenital,Cerebral Palsy, Diplegic, Infantile,Cerebral Palsy, Dyskinetic,Cerebral Palsy, Dystonic-Rigid,Cerebral Palsy, Hypotonic,Cerebral Palsy, Mixed,Cerebral Palsy, Monoplegic, Infantile,Cerebral Palsy, Quadriplegic, Infantile,Cerebral Palsy, Rolandic Type,Cerebral Palsy, Spastic,Congenital Cerebral Palsy,Diplegia, Spastic,Infantile Cerebral Palsy, Diplegic,Infantile Cerebral Palsy, Monoplegic,Infantile Cerebral Palsy, Quadriplegic,Little's Disease,Monoplegic Infantile Cerebral Palsy,Rolandic Type Cerebral Palsy,Athetoid Cerebral Palsy,Atonic Cerebral Palsy,Cerebral Palsies, Athetoid,Cerebral Palsies, Dyskinetic,Cerebral Palsies, Dystonic-Rigid,Cerebral Palsies, Monoplegic,Cerebral Palsy, Dystonic Rigid,Cerebral Palsy, Monoplegic,Diplegias, Spastic,Dyskinetic Cerebral Palsy,Dystonic-Rigid Cerebral Palsies,Dystonic-Rigid Cerebral Palsy,Hypotonic Cerebral Palsies,Hypotonic Cerebral Palsy,Mixed Cerebral Palsies,Mixed Cerebral Palsy,Monoplegic Cerebral Palsies,Spastic Cerebral Palsies,Spastic Cerebral Palsy,Spastic Diplegias
D002658 Developmental Disabilities Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed) Child Development Deviations,Child Development Disorders,Child Development Disorders, Specific,Developmental Delay Disorders,Disabilities, Developmental,Development Disorders, Child,Child Development Deviation,Child Development Disorder,Development Deviation, Child,Development Deviations, Child,Development Disorder, Child,Developmental Delay Disorder,Developmental Disability,Deviation, Child Development,Disability, Developmental
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders

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