Leukocyte Accumulation and Hemodynamic Changes in the Cerebral Microcirculation During Early Reperfusion After Stroke by Leslie S. Ritter, Jose A. Orozco, Bruce M. Coull, Paul F. McDonagh and William I. Rosenblum
This week’s peer-reviewed article
is about the role of leukocyte accumulation and the changes in the flow of
blood after an ischemic stroke, specifically a middle cerebral artery occlusion
reperfusion (MCAO-R).
How were they able to model an MCA stroke?
They used a technique called intraluminal filament method (IFM).
The animal model of choice was the male Sprague-Dawley rats at 250-300g mass,
which were separated into two groups, namely, the sham group (n=7) and the
experimental or MCAO-R group (n=7). They took the rats and anesthetized them
and visualized the right carotid artery by making an incision on the rat’s
neck. The IFM as described on the paper was confusing at first, so I searched
for how this technique is done. I found a video (link below) that showed how
the procedure is done. Basically, once they’ve visualized the common carotid
artery, they tie ligatures on the external carotid artery (ECA) and the common
carotid artery (CCA) to prevent the bleeding. Then they make an incision by the
internal carotid artery (ICA) and insert the nylon filament. For the sham
surgery, they did the exact same thing, but withdrew the nylon filament
immediately. However, for the MCAO-R group, the filament was left for two hours
then was removed. They took a piece of the dura and observed the hemodynamic
changes using a fluorescent microscope.
What did they find out?
- There were no significant statistical difference between the sham and MCAO-R group with regards to gases, blood pressure, body temperature, and body weight.
- In the venules, there were presence of leukocyte adhesion after MCAO-R compared to sham group
- In the arterioles, there were presence of leukocyte adhesions in the MCAO-R only at 30 minutes but not after 15 or 60 minutes
- In the capillaries, leukocyte trapping was greater in the MCAO-R group at 15 and 30 minutes
- Rolling leukocytes were significantly higher in the MCAO-R group compared to the sham group
- There were no significant statistical difference between the sham and MCAO-R group with regards to gases, blood pressure, body temperature, and body weight.
- In the venules, there were presence of leukocyte adhesion after MCAO-R compared to sham group
- In the arterioles, there were presence of leukocyte adhesions in the MCAO-R only at 30 minutes but not after 15 or 60 minutes
- In the capillaries, leukocyte trapping was greater in the MCAO-R group at 15 and 30 minutes
- Rolling leukocytes were significantly higher in the MCAO-R group compared to the sham group
- They talked about the reason why there were high numbers of rolling leukocytes in the MCAO-R group. A part of it was that selectin adhesion molecules and integrins +ICAM-1 ligands are upregulated during an ischemic episode.
- In the case of an ischemic stroke, the endothelial cells of the vessels are stimulated to express selectin surface proteins and leukocytes bind to these with a weak affinity and cause the leukocytes to basically roll. The link below shows a great video of how leukocytes roll. It’s pretty cool!
- Leukocyte plugging in the capillaries could be responsible for the low shear in the MCAO-R group, but it’s still a controversial concept.
Their study was able to show that
there are leukocytes at high levels present during an ischemic stroke, and they
do cause damage once they are activated by releasing toxic mediators, which
will eventually hinder the process of healing. I feel like it's not a surprise that leukocytes are recruited in the ischemic area because it is part of what they do. It was surprising to see and know that they were also responsible to injury after an MCAO-R.
Can you think of other way leukocytes can be dangerous
during recovery from a stroke and reperfusion?
Journal Article Link
Filament MCAO
Leukocyte Rolling
I found a couple of articles that discussed leukocytes' effects during a stroke and MMP's role in ischemic stroke. In the hours to days following an ischemic stroke, infiltrating leukocytes cause the large-scale production of reactive oxygen species and the activation of matrix metalloproteinases (especially MMP-9), which add to the brain's inflammatory responses even more by causing more extensive activation of resident cells and infiltration of leukocytes. MMP-9 is able to degrade major components of the blood brain barrier basal lamina, which is thought to play a role in ischemic stroke. Leukocytes also release many proinflammatory cytokines, which upregulate MMP-9 in endothelial cells, neutrophils, and macrophages.
ReplyDeletehttp://www.jleukbio.org/content/87/5/779.full
http://www.mdbiosciences.com/blog/bid/86499/MMPs-in-ischemic-conditions-stroke-and-myocardial-infarct
Hey Kelly,
DeleteI remember MMPs from cancer biology. I did not know that they play a role in ischemic stroke. I recall MMPs as endopeptidases that help degrade the matrix. This sure sounds like one of the factors that will exaggerate the damage after an ischemic stroke.
I was surprised with the activity of leukocytes. I know that they cause inflammation, but I was not aware that they are more damaging rather than helpful in cases that involve the brain.