JCBFM 0408
All:
A summary of JCBFM, April 2008. 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. HIV-1 activates proinflammatory and interferon-inducible
genes in human brain microvascular endothelial cells: putative mechanisms of
blood–brain barrier dysfunction. Chaudhuri, et al.
Relevance: Very low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600567a.pdf
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*2. Close coupling between astrocytic and neuronal
metabolisms to fulfill anaplerotic and energy needs in the rat brain. Serres, et al.
Sullysummary: Astronauts continue to expore the mystery of
these glial cells. Radioactive carbon (in the form of gluc + acetate) was used
to study metabolism in awake rats and those
anesthetized with phenobarbital. Surprise! Awake
animals animals had higher brain metabolic activity than gorked animals! Other
results indicated that there is significant cross talk between neurons and
astrocytes in the regulation of brain metabolism, depending on brain activity.
Maybe the subtleties of these findings are whoop-dee-doo for the
astrocyte/brain metabolism community, but they don't seem particularly
earth-shattering to me. Am I missing something? Do you care?
Relevance: Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600568a.pdf
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*3. Multivariate and univariate analysis of continuous
arterial spin labeling perfusion MRI in Alzheimer’s
disease. Asllani,
et al.
Relevance: Very Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600570a.pdf
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*4. A concerted role of Na+–K+–Cl cotransporter and Na+/Ca2+
exchanger in ischemic damage. Luol, et al.
Sullysummary: The authors have previously reported that the
activity of the Na+/K+/Cl- transporter, NKCC1, as refleted by protein
phosphorylation, is increased in cortex and striatum during reperferfusion
after transient MCAO in the rat, and that blocking this increased activity,
either pharmacologically or genetically, reduces infarct volume, in strict
accordance with Krause's law. The putative mechanism for this effect is
decreased edema, decreased axonal and astrocytic stress, and inhibition of
excitoxicity-induced "reverse mode" operation of the Na+/Ca++
exchanger (NCX-->NCXrev) during later reperfusion, which causes calcium to
be pumped into cells. (That would be bad.) These findings, however, are not
without controversy: other investigators have found that administration of
several such inhibitors at the time of _permanent_ MCAO worsens the brain
infarct lesion. In the current study, Na+–K+–Cl- cotransporter isoform 1
(NKCC1) and Na+/Ca2+ exchanger isoform 1 (NCX1) were expressed in cortical
neurons. Three hours of OGD increased expression of NCX1 protein, which
remained elevated during 1 to 21 h reoxygenation. Neurons programmed to express
50% less NCX1 protein had 60% less NCX-mediated Ca2+ influx. In
double-heterozygous knockouts for NCX and NKCC1 NCX1+/-/NKCC1+/-) NCX-mediated
Ca2+ influx was virtually abolished, and neuronal survival improved. Moreover,
NCX1+/-/NKCC1+/- mice had significantly reduced infarct volumes at 24 and 72
hours. The authors suggest that NKCC1 in conjuction with NCX1 "plays a
role" in reperfusion-induced brain injury. Hows' that for noncomittal
language? "Plays a role." Yeah, sure, and I
"play a role" in the world economy. So?
Relevance: Medium.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600561a.pdf
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*5. GADD34 gene restores virulence in viral vector used in
experimental stroke study. McCabe1, et al.
Sullysummary: GADD34 is expressed in the ischaemic brain and
reverses protein synthesis shutdown by dephosphorylating eIF2a. In this study,
the authors used a a deficient herpes simplex virus
(HSV) vector to promote GADD34 expression in the mouse brain prior to ischemic
insult. In the animals that got this construct, GADD34 increased infarct
volume. Now, before you get all excited about where this puts us in the
is-restoration-of-protein-synth-good-for-you debate, two things have to be
mentioned: (1) the authors did not measure protein synthesis. (2) GADD34
expression apparently restored HSV virulence, which means that the treated mice
all ended up with a bit of an HSV encephalitis. So. I'm not sure what this all means. Maybe one of you can
read the paper and tell me...
Relevance: HIGH.
Link:
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600565a.pdf
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*6. Matrix metalloproteinase inhibition facilitates cell
death in intracerebral hemorrhage in mouse.
Grossetete and Rosenberg.
Sullysummary: Metaloproteinase-mediated
"gelatinolytic" activity is increased in ICH (Oh, come on! There's
always room for Jell-O!) and exogenous inhibitors of
matrix metalloproteinase may reduce injury. However, an
endogenous inhibitor, TIMP-3, which is "elevated" after ischemia,
"promotes neuronal apoptosis," putatively by potentiating extrinsic
apoptotic signaling. Except that the authors couldn't prove it. They
used a mouse model and ...and ...eyes getting heavy ...can't ...stay ...awake
...must ...finish ...ZZZZZZZZZZZZZ.
Relevance: Low (at best).
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600572a.pdf
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*7. Coupling of angiogenesis and
neurogenesis in cultured endothelial cells and neural progenitor cells after
stroke.
Teng1, et al.
Sullysummary. More
from our buddy Mike Chopp. The guy is just a machine. Wouldn't you like
to be in JCBFM two months in a row? This is an in vitro study, using a
coculture system. The authors demonstrate that cerebral endothelial cells
activated by stroke enhance proliferation and differentiation of neural
progenitors. Conversely, ischemic-stressed neural progenitor cells promoted an
elementary form of angiogenesis. This cross-talk (both ways) was blocked by an
inhibitor of VEGFR. The authors conclude, not unreasonably, that angiogenesis
and neurogenesis are coupled after stroke (in a manner I find shockingly
reminiscent of cancer-induced neogenesis), and that this coupling is mediated
by VEGF. Relevance to us is moderate-to-hi, but the paper is a technical
tour-de-force and worth looking at.
Relevance: Moderate-HIGH.
Linke (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600573a.pdf
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*8. Mitochondrial Ca2+ uniporter blockers influence
activation-induced CBF response in the rat somatosensory cortex
Kannurpatti et al.
Sullysummary:
Ruthenium red (RuR), a nonspecific inhibitor of the mitochondrial
calcium uniporter (MCU), and Ru360, a highly specific inhibitor of the MCU,
were given IV or ICV to investigate the effect on CBF. IV: not so much. ICV: a
hyperemic response response was observed. Bottom line: mitochondrial calcium
signaling seems to mediate neuronal activity-induced changes in vascular tone
and CBF. Makes sense: if a population of neurons is more active and using more
energy, they work their mito more, increase their mito Ca++ signaling, and
signal for more blood flow ("ey! We're working HARD over here! More cheeseburgers!") Obviously, this could have some
implications for CBF in the reperfusion state, especially when the
Relevance: Medium.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600574a.pdf
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*9. Intraluminal thread model of focal stroke in the
non-human primate. Freret1,
et al.
Sullysummary: Marmosets got stroked by MCAO using a
monofilament model. The procedure is described. Strokes were relatively
uniform. Permanent occlusion was worse than transient (the HELL you say!). CBF
measured by LDF and MRI. No cerebral hemorrhage, which is actually important (rat
models are plagued by this complication). Basically, the authors describe a
focal ischemia model which may prove valuable when a nonhuman primate model is
desirable and no Republican senators or lawyers are available. Or, as The Dude
would say: "Awww...nice marmot!"
Relevance: Low-Moderate.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600575a.pdf
Also see: http://www.youtube.com/watch?v=cf3qvF7fABE
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*10. Voltage-gated K+ channel dysfunction
in myocytes from a dog model of subarachnoid hemorrhage. Jahromi, et al.
Relevance: Very Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600577a.pdf
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*12. The rapid decrease in astrocyte-associated dystroglycan
expression by focal cerebral ischemia is protease-dependent.
Milner1, et al.
Relevance: Very Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600585a.pdf
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*13. Reduced cerebral fluoro-L-dopamine
uptake in adult patients suffering from phenylketonuria. Landvogt, et al.
Relevance: Very Low.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600571a.pdf
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*14. Review Article: Mechanistic role of calpains in
postischemic neurodegeneration. Bevers and Neumar.
Sullysummary: State-of-the-art review of our old friend
calpain from our old friend Neumar, with a detailed description of the calpain
system and organellar and biochemical targets. MUST
Relevance: HIGH.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600595a.pdf
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*15. MRI of monocyte infiltration in an
animal model of neuroinflammation using SPIO-labeled monocytes or free USPIO.
Engberink1, et al.
Relevance: Very Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600580a.pdf
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*16. Improving PET receptor binding estimates from
Relevance: Very Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n4/pdf/9600584a.pdf
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END SUMMARY.