Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice
| Autor: | John G. Sled, Elaine Liu, Lisa M. Gazdzinski, Lindsay S. Cahill, Sharon Portnoy, Yu-Qing Zhou, C. David Mazer, Gregory M. T. Hare, Albert K. Y. Tsui, Andrea Kassner |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Ischemia Mice Transgenic Anemia Sickle Cell Brain Ischemia White matter Brain ischemia Mice 03 medical and health sciences 0302 clinical medicine Animals Medicine Gray Matter Hypoxia Brain business.industry Brain Cerebral hypoxia Original Articles Hypoxia (medical) medicine.disease White Matter Sickle cell anemia Stroke Carotid Arteries 030104 developmental biology medicine.anatomical_structure Neurology Cerebral blood flow Cerebral cortex Cerebrovascular Circulation Neurology (clinical) medicine.symptom Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 37:994-1005 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1177/0271678x16649194 |
| Popis: | Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia. |
| Databáze: | OpenAIRE |
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