Spectrum of Short- and Long-Term Brain Pathology and Long-Term Behavioral Deficits in Male Repeated Hypoxic Rats Closely Resembling Human Extreme Prematurity
| Autor: | Liping Goddard, Sarah E. Kohe, Logan J. Voss, David K. Bilkey, Penny Birchall, William Huang, Matthew V. Covey, Dorothy E. Oorschot |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology medicine.medical_specialty Nerve Fibers Myelinated Rats Sprague-Dawley White matter Myelin medicine Sprague dawley rats Animals Hypoxia Maze Learning Myelin Sheath Neurons Radial arm maze Behavior Animal Cerebral white matter General Neuroscience Brain Articles Hypoxia (medical) Rats Oligodendroglia medicine.anatomical_structure Animals Newborn Astrocytes medicine.symptom Volume loss Psychology Neuroscience Absolute volume |
| Zdroj: | Journal of Neuroscience. 33:11863-11877 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0342-12.2013 |
| Popis: | Brain injury in the premature infant is associated with a high risk of neurodevelopmental disability. Previous small-animal models of brain injury attributable to extreme prematurity typically fail to generate a spectrum of pathology and behavior that closely resembles that observed in humans, although they provide initial answers to numerous cellular, molecular, and therapeutic questions. We tested the hypothesis that exposure of rats to repeated hypoxia from postnatal day 1 (P1) to P3 models the characteristic white matter neuropathological injury, gray matter volume loss, and memory deficits seen in children born extremely prematurely. Male Sprague Dawley rats were exposed to repeated hypoxia or repeated normoxia from P1 to P3. The absolute number of pre-oligodendrocytes and mature oligodendrocytes, the surface area and g-ratio of myelin, the absolute volume of cerebral white and gray matter, and the absolute number of cerebral neurons were quantified stereologically. Spatial memory was investigated on a radial arm maze. Rats exposed to repeated hypoxia had a significant loss of (1) pre-oligodendrocytes at P4, (2) cerebral white matter volume and myelin at P14, (3) cerebral cortical and striatal gray matter volume without neuronal loss at P14, and (4) cerebral myelin and memory deficits in adulthood. Decreased myelin was correlated with increased attention deficit hyperactivity disorder-like hyperactivity. This new small-animal model of extreme prematurity generates a spectrum of short- and long-term pathology and behavior that closely resembles that observed in humans. This new rat model provides a clinically relevant tool to investigate numerous cellular, molecular, and therapeutic questions on brain injury attributable to extreme prematurity. |
| Databáze: | OpenAIRE |
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