JCBFM, June 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.
Cerebral autoregulation: an overview of current concepts and methodology with
special focus on the elderly. van Beek,et al.
Immediate Relevance: VERY LOW.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm200813a.pdf
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*2. Brief
Communication: Increase in circulating CD34-positive cells in patients with
angiographic evidence of moyamoya-like vessels. Yoshihara,
et al.
Immediate Relevance:
VERY LOW.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm20081a.pdf
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*3. ROS-independent preconditioning
in neurons via activation of mitoKATP channels by BMS-191095. Gaspar, et al.
Sullysummary: This one is a must-read. I've gone through it twice and plan to do so again. The authors have previously demonstrated that BMS (BMS-191095), a highly selective mitochondrial atp-sensitive potassium (mitoKatp) channel agonist (opens the channel)leads to preconditioned neuroprotection. The selectivitiy of this agent distinguishes it from diazoxide, which has more diverse effect. Studies with diazoxide have led to the conclusion that mitokatp agonists work in part by inducing a surge in ROS, which induce preconditioning. In this study, the authors pretty much put that idea to rest. They don't dispute that ROS can induce preconditioning, but they do show that mitoKatp agonists do not work in this manner. Here, using rat brain mitochondria and rat cortical neuronal cultures they demonstrate that
(1) BMS depolarizes mitochondria WITHOUT increasing ROS.
(2) Long-term BMS treatment of cultured neurons leads to
sustained mitochondrial depolarization and decreased ROS. They speculate that
increased K+ influx through mitoKatp channels may maintain matrix volume and
preserve mitochondrial integrity and allow rapid restoration of energy charge.
Indeed, the authors found high levels of ATP despite mitochondrial
depolarization. This could all fit in with insulin-induced cytoc
phosphorylation, signaling to the ETS, and other components of Maik's work.
(3) BMS activated the PI3K signaling pathway, resulting in
phosphorylation of both Akt and GSk3b, as well as wort-sensitive induction of
catalase transcription.
The paper is worth reading solely for its methods of
mitochondrial investigation, and the section on monitoring free cytosolic
calcium levels may be of interest to Mike (although Thomas now tells me that
Mike sez they're "doing it wrong.") OVerall, this is a paper that
ties together several disparate threads of interest to our lab: mitochondrial dysfunction,
growth factor-PI3K-Akt signaling, and ROS. Take a look.
Immediate Relevance: HIGH.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/9600611a.pdf
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*4. Proliferating
progenitor cells: a required cellular element for induction of ischemic
tolerance in the brain. Maysami, et al.
Sullysummary: The
authors, collaborators from
Immediate Relevance: Medium.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm20084a.pdf
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*5. Neuroprotective
effects of tempol, a catalytic scavenger of peroxynitrite-derived free
radicals, in a mouse traumatic brain injury model. Deng-Bryant,
et al.
Sullysummary:
Tempol is a catalytic scavenger of peroxynitrite-derived free radicals, and in
this study the authors used it to evaluate its efficacy on outcome and several
biochemical endpoints in a TBI model. The results are in complete concordance
with Krause's law, but the authors are hip to the MTA-BRAIN principle. They
conclude: "However, the modest neuroprotective effect of tempol suggests
that multitarget combination trategies may be needed to interfere with
posttraumatic secondary injury to a degree worthy of clinical
translation." Ya think?
The paper is of interest because of its design, techniques
and implication of calpain. The diagram on page 2 is worth the price of
admission, and I like the way the authors set up their dose-response and
window-of-opportunity experiments. Note also the techniques for mitochondrial
assessment. Worth a look.
Immediate Relevance: Medium-HIGH.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm200810a.pdf
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*6. Globus pallidus
stimulation reduces frontal hyperactivity in tardive dystonia. Thobois, et
al.
Immediate Relevance: VERY
LOW.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/9600610a.pdf
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*7. Glucocorticoids
increase VE-cadherin expression and cause cytoskeletal rearrangements in murine
brain endothelial cEND cells. Blecharz, et al.
Immediate Relevance: VERY
LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm20082a.pdf
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*8. Dietary blueberry
supplementation affects growth but not vascularization of neural transplants.
MWillis, et al.
Sullysummary: Eat
your blueberries, dammit!
Immediate Relevance: Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm20083a.pdf
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*9. Brain
redox imaging using blood–brain barrier-permeable nitroxide MRI contrast agent. Hyodo, et al.
Sullysummary:
Would be of more interest, particularly to Anthony, if we had a magnet that
could do this.
Immediate Relevance: Medium-Low.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm20085a.pdf
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*10. Oxidative stress
through activation of NAD(P)H oxidase in hypertensive
mice with spontaneous intracranial hemorrhage. Wakisaka,
et al.
Sullysummary: The
authors, working in the flooded cornfields of
Immediate Relevance: Low.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm20087a.pdf
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*12. Overexpression
of UCP2 protects thalamic neurons following global ischemia in the mouse. Olsson, et al.
Sullysummary: This ties in with something I first encountered while
reading one of Gary Fiskum's reviews on mitochondrial dysfunction in brain
ischemia. In that paper, Gary talked about how "mild uncoupling" of
electron transport from oxidative phosphorylation could be neuroprotective, by
limiting expression of ROS and promoting salutary balance between the
NAD+/NADPH pools. A family of uncoupling proteins, coded for by nuclear DNA and
residing on the inner membrane, is known to exist. Uncoupling protein 2 (UCP2)
is upregulated in the brain after sublethal ischemia, and overexpression of
UCP2 is neuroprotective in several models of neurodegenerative disease. The
authors induced overexpression of UCP2 in mice and decreased neuronal damage in
areas where UCP2 upregulation was highest (primarily thalamus). No actual
evaluation of mitochondrial membrane potential, ROS production, or NAD+/NADPH
ratio diminishes my enthusiasm for this paper.
Immediate Relevance: Medium.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm20089a.pdf
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*13. Endothelial
nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral
vasospasm after aneurysmal subarachnoid hemorrhage. Starke,
et al.
Immediate Relevance: VERY
LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm200811a.pdf
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*14. Toward safer
thrombolytic agents in stroke: molecular requirements for NMDA
receptor-mediated neurotoxicity. Lopez-Atalaya, et al.
Sullysummary: This has relevance for our MTA-BRAIN and focal
ischemia work. The authors demonstrate that tPA binds
to actually CLEAVES the amino-terminal domain of NMDA glutamate receptors,
INCREASING calcium flux. Somebody correct me if I'm wrong, but in terms of
stroke therapy, that seems rather not the point. This underscores something
I've been bitching about for a long time: thrombolysis is a good idea on paper,
but in practice it presents us with a therapeutic margin so narrow as to render
the therapy positively dangerous. Until we can limit the collateral damage of tPA and increase the therapeutic margin (ie, with adjuvant
neuroprotectants to limit reperfusion injury), this approach remains incredibly
risky, and its current status as the standard of care is, in my opinion,
inappropriate. The authors suggest that a new generation of safer thrombolytics
is required. Ya think?
Immediate Relevance:
Medium-HIGH.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm200814a.pdf
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*15. Coordinated
nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II
metabolizing enzyme, GSTp, at the blood–brain barrier. Bauer, et al.
Immediate Relevance: VERY
LOW.
Link (PDF): http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm200816a.pdf
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*16. Nasal
administration of osteopontin peptide mimetics confers neuroprotection in
stroke. Doyle, et al.
Sullysummary:
More on the intranasal administration of neuroprotectants (remember the guys
who gave IGF-1 this way). It would be interesting to know how this worked in
humans, if at all.
Immediate Relevance: Low.
Link (PDF):
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*16. Detection of
phosphorylated NF-H in the cerebrospinal fluid and blood of aneurysmal
subarachnoid hemorrhage patients
Lewis, et al.
Immediate Relevance: VERY
LOW.
Link (PDF):
http://www.nature.com/jcbfm/journal/v28/n6/pdf/jcbfm200812a.pdf
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END SUMMARY.