[HTML][HTML] Prolonged blood-brain barrier injury occurs after experimental intracerebral hemorrhage and is not acutely associated with additional bleeding

CA Nadeau, K Dietrich, CM Wilkinson… - Translational stroke …, 2019 - Springer
CA Nadeau, K Dietrich, CM Wilkinson, AM Crawford, GN George, HK Nichol, F Colbourne
Translational stroke research, 2019Springer
Intracerebral hemorrhage (ICH) causes blood-brain barrier (BBB) damage along with
altered element levels in the brain. BBB permeability was quantified at 3, 7, and 14 days with
Evans Blue dye after collagenase-induced ICH in rat. At peak permeability (day 3), a
gadolinium (Gd)-based contrast agent was injected to further characterize BBB disruption,
and X-ray fluorescence imaging (XFI) was used to map Gd, Fe, Cl, and other elements. XFI
revealed that Ca, Cl, Gd, and Fe concentrations were significantly elevated, whereas K was …
Abstract
Intracerebral hemorrhage (ICH) causes blood-brain barrier (BBB) damage along with altered element levels in the brain. BBB permeability was quantified at 3, 7, and 14 days with Evans Blue dye after collagenase-induced ICH in rat. At peak permeability (day 3), a gadolinium (Gd)-based contrast agent was injected to further characterize BBB disruption, and X-ray fluorescence imaging (XFI) was used to map Gd, Fe, Cl, and other elements. XFI revealed that Ca, Cl, Gd, and Fe concentrations were significantly elevated, whereas K was significantly decreased. Therefore, using Gd-XFI, we co-determined BBB dysfunction with alterations in the metallome, including those that contribute to cell death and functional outcome. Warfarin was administered 3 days post-ICH to investigate whether additional or new bleeding occurs during peak BBB dysfunction, and hematoma volume was assessed on day 4. Warfarin administration prolonged bleeding time after a peripheral cut-induced bleed, but warfarin did not worsen hematoma volume. Accordingly, extensive BBB leakage occurred after ICH, but did not appear to affect total hematoma size.
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