Seizures are associated with brain injury severity in a neonatal model of hypoxia–ischemia

• Published in: Neuroscience 2010-03, Vol.166 (1), p.157-167
• Main Authors: Björkman, S.T, Miller, S.M, Rose, S.E, Burke, C, Colditz, P.B
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Brain - metabolism; Brain - pathology; Brain - physiopathology; brain damage; Diffusion; Disease Models, Animal; Disease Progression; Electroencephalography; Epilepsy - etiology; Epilepsy - pathology; Epilepsy - physiopathology; Evoked Potentials - physiology; Fundamental and applied biological sciences. Psychology; Hypoxia, Brain - complications; Hypoxia, Brain - pathology; Hypoxia, Brain - physiopathology; Hypoxia-Ischemia, Brain - complications; Hypoxia-Ischemia, Brain - pathology; Hypoxia-Ischemia, Brain - physiopathology; hypoxia–ischemia; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; neonatal seizures; Nerve Degeneration - etiology; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Neurology; Severity of Illness Index; Sus scrofa; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.11.067

Abstract Hypoxia–ischemia is a significant cause of brain damage in the human newborn and can result in long-term neurodevelopmental disability. The loss of oxygen and glucose supply to the developing brain leads to excitotoxic neuronal cell damage and death; such over-excitation of nerve cells can also manifest as seizures. The newborn brain is highly susceptible to seizures although it is unclear what role they have in hypoxic-ischemic (H/I) injury. The aim of this study was to determine an association between seizures and severity of brain injury in a piglet model of perinatal H/I and, whether injury severity was related to type of seizure, i.e. sub-clinical (electrographic seizures only) or clinical (electrographic seizures+physical signs). Hypoxia (4% O2 ) was induced in anaesthetised newborn piglets for 30 min with a final 10 min period of hypotension; animals were recovered and survived to 72 h. Animals were monitored daily for seizures both visually and with electroencephalogram (EEG) recordings. Brain injury was assessed with magnetic resonance imaging (MRI),1 H-MR spectroscopy (1 H-MRS), EEG and by histology (haematoxylin and eosin). EEG seizures were observed in 75% of all H/I animals, 46% displayed clinical seizures and 29% sub-clinical seizures. Seizure animals showed significantly lower background amplitude EEG across all post-insult days. Presence of seizures was associated with lower cortical apparent diffusion coefficient (ADC) scores and changes in1 H-MRS metabolite ratios at both 24 and 72 h post-insult. On post-mortem examination animals with seizures showed the greatest degree of neuropathological injury compared to animals without seizures. Furthermore, clinical seizure animals had significantly greater histological injury compared with sub-clinical seizure animals; this difference was not apparent on MRI or1 H-MRS measures. In conclusion we report that both sub-clinical and clinical seizures are associated with increased severity of H/I injury in a term model of neonatal H/I.