Download hepcidin crosses the blood-brain barrier in systemic inflammation

Hepcidin crosses the blood-brain barrier in systemic inflammation, after
mechanical injury and participates in glial scar formation and
regeneration.
A. Raha 1,2, J. Zhao1, J. Marland1, A. Bomford3 and R. Raha-Chowdhury1*.
1Cambridge
Centre for Brain Repair, Department of Clinical
Neuroscience, 2Department of Medicine, University of Cambridge, UK.
3Institute of Liver Studies, King’s College London School of Medicine,
London, UK.
Supported by/grant awarding body: MRC and Scholl Foundation
There is extensive evidence that iron homeostasis break down occurs in the
brain and that iron plays a role in the pathogenesis of a wide spectrum of
neurological disorders including Alzheimer’s disease (AD) and Parkinson’s
disease. Inflammatory processes have been implicated in both acute (Spinal
cord injury, stroke) and chronic neurodegenerative diseases.
Hepcidin expression is increased in the brain during systemic inflammation
but currently it is not known how hepcidin contributes to brain iron
homeostasis and inflammation.
We investigated a role for hepcidin in the brain after acute inflammation and
brain injury in in vivo and in vitro models. Firstly, lipopolysaccharide was
administered into the intraperitoneal cavity of adult rats to investigate acute
inflammation at the whole body level while mechanical brain injury was
performed to examine the effect of focal injury to brain tissue. Secondly, we
generated various primary neuronal and glial cultures to investigate the
function of hepcidin in vitro.
Hepcidin does not originate in situ in the brain, since little hepcidin mRNA was
detectable in the brain, rather it was synthesised systemically in the liver and
crosses the blood brain barrier. After brain injury hepcidin was expressed in a
small population of astrocytes, neurons and vascular endothelium but rarely
found in microglia. A dramatic increase in hepcidin expression was seen after
acute stab injury and was localised in close proximity to the glial scar.
Our data suggests that hepcidin has a role modulatory in enhancing glial and
neuronal proliferation after acute injury. Finally, we compared hepcidin protein
expression in human control and AD brain with an established transgenic
mouse model for AD. Hepcidin expression was noted in close to amyloid
plaques in both neurons and astrocytes. Understanding the mechanism of
action of hepcidin in neurodegeneration could lead to novel therapeutic
strategies.