Increased brain hemopexin levels improve outcomes after intracerebral hemorrhage

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Jenna L LeclercSylvain Doré

Abstract

Following intracerebral hemorrhage (ICH), extracellular heme precipitates secondary brain injury, which results in irreversible brain damage and enduring neurological deficits. Hemopexin (Hpx) is an endogenous protein responsible for scavenging heme, thereby modulating its intrinsic proxidant/proinflammatory properties. Although Hpx is present in the brain, the endogenous levels are insufficient to combat the massive heme overload following ICH. We hypothesized that increasing brain Hpx levels would improve ICH outcomes. Unique recombinant adeno-associated viral vectors were designed to specifically overexpress Hpx within the mouse brain. Western blotting, ELISA, and immunohistochemistry of brain homogenates/sections, CSF, and serum were performed. As compared to controls, Hpx mice have increased Hpx protein levels in all three types of biospecimens evaluated, which results in 45.6 ± 6.9% smaller lesions and improved functional recovery after ICH (n=14-19/group, p < 0.05). Local mechanistic analyses show significantly less tissue injury, trends toward smaller hematoma volumes, unchanged heme oxygenase 1 and iron levels, and significantly increased microgliosis and decreased astrogliosis and lipid peroxidation. Peripheral levels...Continue Reading

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Citations

Mar 31, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jenna L LeclercSylvain Doré
Mar 4, 2018·Journal of Neurochemistry·Jing Chen-RoetlingRaymond F Regan
Jun 22, 2018·Nature Reviews. Neurology·Diederik BultersIan Galea
Aug 27, 2017·Scientific Reports·Abdullah Shafique AhmadSylvain Doré
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Feb 6, 2021·Neuroscience and Biobehavioral Reviews·Deborah ChiabrandoEmanuela Tolosano
Apr 8, 2021·Stroke; a Journal of Cerebral Circulation·Luiz Ricardo C VasconcellosPedro Moreno Pimentel-Coelho
Feb 14, 2021·Biological Chemistry·Milena Sophie DetzelDiana Imhof

Datasets Mentioned

BETA
BC019901

Methods Mentioned

BETA
PCR
electrophoresis
ELISA

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