Lesion size is exacerbated in hypoxic rats whereas hypoxia-inducible factor 1 alpha and vascular endothelial growth factor increase in injured normoxic rats: a prospective cohort study of secondary hypoxia in focal traumatic brain injury.

Autor: Eric Peter Thelin, Arvid eFrostell, Jan eMulder, Nicholas eMitsios, Peter eDamberg, Sahar Nikkhou Aski, Mårten eRisling, Mikael eSvensson, Cristina eMorganti-Kossmann, Bo-Michael eBellander
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Frontiers in Neurology, Vol 7 (2016)
Druh dokumentu: article
ISSN: 1664-2295
DOI: 10.3389/fneur.2016.00023
Popis: Background: Hypoxia following traumatic brain injury (TBI) is a severe insult shown to exacerbate the pathophysiology, resulting in worse outcome. The aim of this study was to investigate the effects of a hypoxic insult in a focal TBI model by monitoring brain edema, lesion volume, serum biomarker levels, immune cell infiltration, as well as the expression of hypoxia-inducible factor 1-alpha (HIF-1α and vascular endothelial growth factor (VEGF).Material and methods: Female Sprague-Dawley rats (n=73, including sham and naïve) were used. The rats were intubated and mechanically ventilated. A controlled cortical impact device created a 3 millimeter deep lesion in the right parietal hemisphere. Post injury, rats inhaled either normoxic (22% O2) or hypoxic (11% O2) mixtures for 30 minutes. The rats were sacrificed at 1, 3, 7, 14 and 28 days post-injury. Serum was collected for S100B measurements using ELISA. Ex-vivo magnetic resonance imaging (MRI) was performed to determine lesion size and edema volume. Immunofluorescence was employed to analyze neuronal death, changes in cerebral macrophage- and neutrophil infiltration, microglia proliferation, apoptosis, complement activation (C5b9), IgG extravasation, HIF-1α and VEGF.Results: The hypoxic group had significantly increased blood levels of lactate and decreased pO2 (p
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