Summary of
JCBFM, September 2008.
You can find all the JCBFM summaries in web
format at:
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.
Also, I must confess that this last month I got
behind on journal club. So that I do not get farther behind, I punted on the
last two articles of relevance, and instead of a Sullysummary I have reproduced
the abstracts. You'll live.
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*1. Quantification
of poly(ADP-ribose)-modified proteins in cerebrospinal
fluid from infants and children after traumatic brain injury. Ericka L
Fink, et al.
Sullysummary: The quest for blood
and csf markers goes on. It's like the holy frippin'
grail. These guys took 17 kids with TBI and 15 controls and showed that a
simple ELISA assay could detect increased PARP in kids with head bonks. There
was no correlation with clinical scoring systems, mechanism of injury, or
outcome.
Immediate
Relevance:
Low
Link
(PDF):
http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200852a.pdf
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*2. Neural
stem/progenitor cells promote endothelial cell morphogenesis and protect
endothelial cells against ischemia via HIF-1a-regulated VEGF signaling. Tamara Roitbak, et al.
Sullysummary:
This is
a huge paper, a technical tour-de-force. In fact, it gives me the impression of
a paper that was intended for Science or Nature but didn't make it. It builds
on other work we've seen recently, including a Chopp paper recently reviewed in
this journal club, indicating a reciprocal relationship between neurogenenesis
and neural stem migration and angiogenesis. Here, the authors delved deeper
into the relationship between neural stem/progenitor cells (NSPCs) and
endothelial cells (ECs) both in vivo and in vitro. They demonstrate that (1)
NSPCs promote EC morphogenesis and prevent EC death after serum starvation and
OGD; (2) HIF-1a and VEGF are both constituitively expressed by NSPFs, with
increased expression of both species after OGD; (3) blocking VEGF blocks
survival (big surprise); and (4) NSPFs promote neovascularization after mild
focal ischemia when transplanted into the mouse.
I have some quibbles with this study. The issue
with HIF-1a is a bit fuzzy--are the authors reporting increased expression of
HIF-1a or decreased destruction? We don't know. THEY don't know. And the way
they set up the time course was a bit suspect. At 3 days after transplantation,
mice were EITHER killed or subjected to MCAO. Stroked mice were reperfused for
3 days and then killed. Unless I'm missing something, that sounds like a way to
end up comparing 3d animals to 6 day animals. Since what the authors were
looking for was neoangiogenesis, that seems like a big deal.
Overall, though, I think it's
right, and this paper underscores something we've known for a long time but
sometimes tend to ignore. We are a farily neurocentric lab, but at the end of
the day what we're trying to repair is a tissue, not a cell type.
Immediate
Relevance:
Low-Medium.
Link
(PDF):
http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200838a.pdf
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*3. Overexpression
of netrin-1 induces neovascularization in the adult mouse brain. Yongfeng
Fan,et al.
Immediate
Relevance:
VERY LOW.
Link
(PDF): http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200839a.pdf
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*4. Combined
therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates
neurogenesis after transient focal cerebral ischemia in rats. Elise Esneault, et al.
Sullysummary:
Yet
another potential model for the design of a combined therapy study. In this
case, the authors combine erythropoieten and neural cell precursor therapy.
Immediate
Relevance: Medium.
Link
(PDF): http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200840a.pdf
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*5.
Necrostatin-1 reduces histopathology and improves functional outcome after
controlled cortical impact in mice. Zerong You, et al.
Sullysummary: Necroptosis is a word
I thought I made up for our syllabus. Actually, it is a type of
"programmed necrosis" mediated by TNFa and Fas. We've known for some
time now, of course, that necrosis was not the purely thermodynamic splat we
used to think it was. Necrostatin-1 is a specific inhibitor of necroptosis that
reduces ischemic tissue damage in experimental stroke models. The authors
hypothesized that necrostatin-1 would reduce histopathology and improve outcome
in mice after injury with a TBI model. Necrostatin did all kinds of good stuff
for these head-bonked mice, including improved MWM performance. The authors
then, rather amazingly, go on to deduce that, because necrostatin worked, that
must mean TBI has a strong necrotic component. I tell ya, people just never
learn.
Immediate
Relevance: Medium.
Link
(PDF): http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200844a.pdf
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*6. Suppression of stroke-induced progenitor proliferation in adult
subventricular zone by tumor necrosis factor receptor 1.
Robert E Iosif, et al.
Abstract: Stroke induced by middle
cerebral artery occlusion leads to transiently increased progenitor
proliferation in the subventricular zone (SVZ) and long-lasting striatal
neurogenesis in adult rodents. Tumor necrosis factor-a (TNF-a) is upregulated
in stroke-damaged brain. Whether TNF-a and its
receptors influence SVZ progenitor proliferation after stroke is unclear. Here
we show that the increased proliferation 1 week after stroke occurred
concomitantly with elevated microglia numbers and TNF-a and
TNF receptor-1 (TNF-R1) gene expression in the SVZ of wild-type mice. TNF
receptor-1 was expressed on sorted SVZ progenitor cells from nestin-green
fluorescent protein reporter mice.In animals lacking TNF-R1, stroke-induced SVZ
cell proliferation and neuroblast formation were enhanced. In contrast,
deletion of TNF-R1 did not alter basal or status epilepticus-stimulated cell
proliferation in SVZ. Addition of TNF-a reduced the size and numbers of SVZ
neurospheres through
a TNF-R1-dependent
mechanism without affecting cell survival. Our results provide the first
evidence that TNF-R1 is a negative regulator of stroke-induced SVZ progenitor
proliferation. Blockade of TNF-R1 signaling might be a novel strategy to
promote the proliferative response in SVZ after stroke.
Immediate Relevance: Medium
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200847a.pdf
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*7.Upregulated
expression of toll-like receptor 4 in monocytes correlates with severity of
acute cerebral infarction. Qing-wu Yang, et al.
Abstract: In the present study,
we observed the expression of toll-like receptor 4 (TLR4) and its downstream
signal pathway in peripheral blood monocytes (PBMs) from patients with acute
cerebral infarct (ACI). The expression of TLR4 and MyD88 by PBMs was determined
by flow cytometry and reverse transcriptase-polymerase chain reaction, and
nuclear factor-jB (NF-jB) activity was detected by electrophoretic mobility
shift assay. Ischemia/reperfusion injury-induced cerebral edema, infarction
area, and neurologic
impairment scores were determined in MyD88 gene knockout mice. The results
indicated a significant increase in circulating TLR4+ monocytes in ACI patients
as compared with the control group and the transient ischemia attack (TIA)
group. This change paralleled an elevation in TLR4mRNA transcription and serum
tumor necrosis factor-a (TNF-a) and interleukin (IL)-6 in the ACI and TIA
groups. Correlation analysis showed TLR4 expression to significantly correlate
with
cytokine levels and stroke
severity. MyD88mRNA differed insignificantly among the three groups. Compared
with wild-type mice, 6 h of cerebral ischemia followed by 24 h of reperfusion
did not significantly change cerebral edema, cerebral infarction area, and
neurologic impairment scores in MyD88 gene knockout mice. Compared with the
control group, serum heat shock protein (HSP) 60 increased significantly in the
ACI and TIA groups, leading to NF-jB activation in TLR4/CD14-transfected HEK293
cells. It is suggested that upregulated TLR4 expression on PMBs may act as one
of the peripheral mechanisms of inflammatory injury after ACI. Moreover,
circulating HSP60 may be a ligand for TLR4, which is involved in the peripheral
mechanism of inflammatory injury after ACI, possibly through an
MyD88-independent signal pathway.
Immediate
Relevance: Medium-HIGH.
Link
(PDF):
http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200850a.pdf
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*8. Experimental and theoretical studies of oxygen gradients in rat
pial microvessels. Maithili Sharan, et al.
Immediate
Relevance: VERY
LOW.
Link
(PDF):
http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200851a.pdf
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*9. Cerebellar autoregulation dynamics in humans. Matthias Reinhard, et
al.
Immediate
Relevance:
VERY LOW.
Link
(PDF):
http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200848a.pdf
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*10. Differential progression of magnetization transfer imaging changes
depending on severity of cerebral hypoxic–ischemic injury. Ursula
I Tuor et al.
Immediate
Relevance:
VERY LOW
Link
(PDF): http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200849a.pdf
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*12. Comparison of noninvasive quantification methods of in vivo
vesicular acetylcholine transporter using [123I]-IBVM SPECT imaging. O Barret.
Immediate
Relevance: VERY
LOW
Link
(PDF):
http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200853a.pdf
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*13. Microhemorrhages in nonfatal high-altitude cerebral edema. Kai Kallenberg, et al.
Immediate
Relevance: VERY
LOW.
Link
(PDF): http://www.nature.com/jcbfm/journal/v28/n9/pdf/jcbfm200855a.pdf
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END
SUMMARY.