title: Correlation between clinical and histologic findings in the human neonatal hippocampus after perinatal asphyxia.
abstract: Hypoxic ischemic encephalopathy after perinatal asphyxia is a major cause of mortality and morbidity in infants. Here, we evaluated pathologic changes in the hippocampi of a cohort of 16 deceased full-term asphyxiated infants who died from January 2000 to January 2009. Histochemical and immunocytochemical results for glial and neuronal cells were compared between cases with or without seizures and to adult and sudden infant death syndrome cases (n = 3 each). All asphyxiated infants displayed neuronal cell damage and reactive glial changes. Strong aquaporin-4 immunoreactivity was seen on astroglial cells within hippocampi in 50% of cases. In patients with seizures, the expression of metabotropic glutamate receptors was increased in glial cells. Cases with seizures displayed increased microglial activation and greater expression of the inflammatory markers interleukin 1β and complement 1q compared with those in cases without seizures. All cases with seizures displayed alterations in the blood-brain barrier, as assessed by immunohistochemistry for albumin. These findings confirm the complex cascade of cellular and molecular changes occurring in the human neonatal hippocampus after perinatal asphyxia. These changes may contribute to seizure development leading to secondary brain damage. These data may aid in the development of therapeutic targets for neonatal seizures.
authors.affiliation: From the Departments of Neonatology (IAMS, TRdH) and Pediatric Neurology (J-MFN), Emma Children's Hospital, Academic Medical Center; and Departments of Clinical Neurophysiology (JHK), Radiology (CBLMM, LR), and (Neuro)Pathology (EA), Academic Medical Center, Amsterdam; SEIN-Stichting Epilepsie Instellingen Nederland, Heemstede (EA); and Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam (EA), The Netherlands.
authors.forename: Irene A M
authors.initials: IA
authors.lastname: Schiering
authors.forename: Timo R
authors.initials: TR
authors.lastname: de Haan
authors.forename: Jikke-Mien F
authors.initials: JM
authors.lastname: Niermeijer
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Koelman
authors.forename: Charles B L M
authors.initials: CB
authors.lastname: Majoie
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
mesh_terms: D051401:Aquaporin 4 / Q000378:metabolism; D001238:Asphyxia Neonatorum / Q000473:pathology* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D015331:Cohort Studies; D015922:Complement C1q / Q000378:metabolism; D004569:Electroencephalography; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007231:Infant, Newborn; D007362:Intensive Care Units / Q000706:statistics & numerical data; D053583:Interleukin-1beta / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012640:Seizures / Q000209:etiology / Q000473:pathology
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D006684:HLA-DR Antigens; D053583:Interleukin-1beta; D018094:Receptors, Metabotropic Glutamate; D015922:Complement C1q; D053148:Caspase 3