JCBFM, May 2008.
You can find all the JCBFM summaries in web format at:
http://sullydog.com/sullysites/jclub/
All articles are listed. My relevance assessment is entirely
implicit and is designated with regard to work we are doing or contemplating
RIGHT NOW. The relevance of an article might change in the future. Those papers
with relevance rated VERY LOW do not
get a Sullysummary.
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*1. Review Article:
Acute neurodegeneration and the inflammasome: central processor for danger
signals and the inflammatory response? George Trendelenburg
Sullysummary: I think you should check this out if you have
the chance, if only to get up to speed on a buzzword you're likely to be
hearing a lot about. When they talk about the inflammasome, they're talking
about something very similar to the apoptosome, only a LOT more elaborate.
Basically, here's the story: after injury, damage-associated molecular patterns
(DAMPs) activate Toll-like receptors (TLRs) that promote the assemply of an
inflammasome complex. These DAMPs include hyaluronin, HSPs, IFN-a, fibronectin,
and cardiolipin (!). THe inflammasome that is activated by these DAMPs via the
TLRs incorporates caspace-1, and its activation is essential for hte
caspase-mediated processing of interleukin-1 and IL-18. Activation of the
inflammasome is associated with both cell death and neuroprotection, depending
on how things balance on the knife edge. Of course, I'm vastly oversimplifying
things, so scan the article for yourself. The
immediate relevance for us is moderate, but it may end up having high relevance
for Karin's myocardial model and our nascent focal ischemia model.
Relevance: Medium-HIGH
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600609a.pdf
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*2. Brief
Communication: Verification of enhancement of the CSF space, not parenchyma, in
acute stroke patients with early blood–brain barrier disruption. Henning, et al.
Relevance: VERY LOW.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600598a.pdf
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*3. Brief
Communication Optimal definition for PWI/DWI mismatch in acute ischemic stroke
patients. Kakuda et al.
Sullysummary: This is a clinical MRI study. It identified a
ration of perfusion-weighted imaging to diffusion-weighted imagint that seemed
to identify which patients would do better with t-PA. May
have some relevance for Anthony and Yours Truly as we go forward into rat
Relevance: Medium
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600604a.pdf
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*4. Transient focal
cerebral ischemia induces a dramatic activation of small ubiquitin-like
modifier conjugation. Yang et al.
Sullysummary: Sumoylation, a post-translational modification
by SUMO (small ubiquitin-like modifer) proteins, is massively activated after
transient forebrain ischemia. Similar to ubiquination...but
different. The authors don't actually talk about the nitty-gritty of
sumoylation, so I did some digging. In contrast to ubiquitin, SUMO is not used
to tag proteins for degradation. Mature SUMO is produced when the last four
amino acids of the C-terminus have been cleaved off. SUMO modification of
proteins has many functions. Among the most frequent and best studied are protein stability, nuclear-cytosolic transport,
transcriptional regulation (mostly transcriptional repression). As opposed to
poly-ubiquitin modification which targets proteins for degradation, SUMOylation
increases a protein's lifetime. It can also change a protein's location in the
cell.The response of SUMO 2/3 proteins in this study really does warrant the
word "massive." The authors, in the discussion, mention the role of
sumoylation in hibernating rodents (squirrels, sleeping republicans), which
gets me thinking. Sumoylation is supposedly a protective response. Wonder what
happens in hypothermia? Might be worth a look.
Anthony?
Relevance: Medium.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600601a.pdf
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*5. Autophagy
after experimental intracerebral hemorrhage. He et al.
Sullysummary: Ah, the new buzzword: ah-TAH-fuh-jee. This
study was focused on ICH, using a very crude but, I must say, relevant model of
intracerebral hemorrhage (take blood from rat, inject blood into brain tissue).
The paper is of interest primarily for the assays the authors used: conversion
of microtubule-associated protein light chain-3 (LC3) from LC3-I to LC3-II, a marker
of the autophagosome, and expression of cathepsin D, a lysosomal biomarker. The
authors also used EM to look at typical ultrastructural changes. In a related
experiment, they demonstrate that it's not blood per se, but iron that appears
to be the culprit. Worth a look.
Relevance: Medium
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600578a.pdf
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*6. Gamma-aminobutyric
acid modulates local brain oxygen consumption and blood flow in rat cerebellar
cortex. Caesar et al.
Relevance: VERY LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600581a.pdf
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*7. Cerebral
blood flow autoregulation in experimental liver failure. Dethloff et al.
Relevance: VERY LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600589a.pdf
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*8. Inhibition of Ih in striatal cholinergic interneurons early after
transient forebrain ischemia. Deng et al.
Relevance: VERY LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600582a.pdf
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*9. Cerebral blood
volume quantification in a C6 tumor model using gadolinium per (3,6-anhydro) a-cyclodextrin as a new magnetic resonance
imaging preclinical contrast agent. Lahrech, et al.
Relevance: VERY LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600602a.pdf
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*10. Mannose binding
lectin gene deficiency increases susceptibility to traumatic brain injury in
mice. Yager et al.
Relevance: VERY LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600605a.pdf
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*12. Toll-like
receptor 9: a new target of ischemic preconditioning in the brain. Stevens
et al.
Sullysummary: This is one you might want to look at after
reading the review on the inflammasome in this same issue. In accordance with
Krause's law, TLR9 ligand reduced infarct volume in an MCAO
model, and implicate this receptor system in TNF-mediated
preconditioning-neuroprotection.
Relevance: Low.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600606a.pdf
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*13. C3a receptor
modulation of granulocyte infiltration after murine focal cerebral ischemia is
reperfusion dependent. Ducruet et al.
Relevance: VERY LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600608a.pdf
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*14. Measurement of
striatal and extrastriatal dopamine transporter binding with high-resolution
PET and [11C]PE2I: quantitative modeling and
test–retest reproducibility. Hirvonen et al.
Relevance: VERY LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n5/pdf/9600607a.pdf
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END SUMMARY.