Jake Pushie

University of Saskatchewan

ABSTRACT

Metabolic Imaging of Brain Hemorrhage

M Jake Pushie,1 Miranda Messmer,1 Nicole J Sylvain,1 Jonathan Heppner,1 Julia Newton,1

Huishu Hou,1 Mark J Hackett,2 Michael E Kelly,1 Lissa Peeling1

1 - Neurosurgery, University of Saskatchewan, Saskatoon, SK, Canada

2 - Curtin University, Perth, WA, Australia

Stroke is a leading cause of death and permanent disability around the world. A major problem

in the characterization of animal stroke models is the potential for hemorrhagic transformation.

Ischemic stroke is caused by loss of blood flow in a region of brain tissue supplied by the

occluded vessel, starving that region of vital O2 and nutrients. Intracerebral hemorrhage (ICH) is

a bleed which occurs in the brain due to blood-brain barrier (BBB) breakdown and accounts for

approximately 15% of all human strokes. We observe 10-20% of our stroke surgeries have

evidence of hemorrhagic transformation. Characterizations of stroke models is challenging due

to the variability introduced by hemorrhagic transformation. We hypothesize that much of the

variability we observe after hemorrhage is due to the fact that we do not know precisely when

the hemorrhagic transformation occurred - resulting in widely varying post-hemorrhage times.

Following ICH, erythrocytes can survive from 2-10 days. Erythrolysis releases oxyhemoglobin,

which is slowly converted to deoxyhemoglobin and subsequently undergoes spontaneous

oxidation to methemoglobin. Further breakdown liberates heme-Fe. In the presence of O2 Fe can

generate free radicals, causing oxidative damage. To protect against oxidative damage

responding microglial cells begin to sequester Fe as ferritin, and therefore at late post-ICH time

points most Fe will be stored in glial cells as ferritin.

In early 2020 our laboratory was temporarily shutdown and we were unable to complete ongoing

experiments. Instead, we embarked on a survey of all stroke imaging data acquired by the

team since 2016, with the goal of better-characterizing ICH. We were able to identify trends,

allowing us to differentiate hemorrhage from ischemic tissue, and differentiate these from blood

vessels, grey and white matter, and from the penumbra − a region of damaged tissue surrounding

the infarct that is the target of stroke treatment. Fe K-edge μ-X-ray absorption spectroscopy

shows that Fe-ferritin can be detected in some samples within the heme-rich hemorrhage.

Sequestration of Fe within ferritin, combined with the concentration of adjacent lipid

peroxidation markers, may be useful markers to date the age of hemorrhages, allowing us to

calculate when a bleed initiated. We have recently established an ICH model to control time of

hemorrhage, allowing us to carry out blinded studies on the feasibility of dating time-of-bleedonset

in a controlled manner.

Poster Session Link:

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If you have any questions for the presenter, please contact them by either one of the following ways:

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Email: jake.pushie@usask.ca