JCBFM 0308

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*1. Spared caudal brainstem SERT binding in early Parkinson’s disease. Albin et al.

 

Relevance: Very Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600599a.pdf

 

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*2. Circulating CD34-positive cells provide a marker of vascular risk associated with cognitive impairment.

Taguchi et al.

 

Sullysummary: CD34+ cells are immature marrow-derived cells that appear to have some importance in maintaining cerebrovascular health, probably through involvment in endothelial repair. Here, the authors present data suggesting that the level of these cells in circulating plasma is correlated with cognitivie impairment in patients with cerebrovascular disease--but not with Alzheimer's patients who had no evidence of ischemia. They propose that the level of circulating CD34+ cells provides a marker of vascular risk associated with cognitive impairment, and that differences in the pathobiology of Alzheimer’s- and vascular-type cognitive impairment may be mirrored in levels of circulating CD34+ cells in these patient populations.

 

Relevance: Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600541a.pdf

 

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*3. Lipocalin 2 is a choroid plexus acute-phase protein. Marques et al.

 

Relevance: Very Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600557a.pdf

 

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*4. Oxygen and glucose deprivation-induced changes in astrocyte membrane potential and their underlying mechanisms in acute rat hippocampal slices.

 

Xie et al.

 

Sullysummary: The role of astrocytes in cerebral ischemia is unclear. (Actually, the role of astrocytes in _everything_ is unclear--they probably play an important role in cognition.) We do know that by about 8 min of ischemia astrocytes undergo a three-phase depolarization, and the relative contributions of ecf K+, neurotransmitters and energy failure in these processes is unclear. The authors, using an OGD/hippocampal slice model with sharp pipette recordings, show that astrocytes respond reversibly to more > 30 mins oxygen and glucose deprivation

(OGD) treatment with multiphasic depolarized membrane potentials (Vm): an 11 mins small-amplitude depolarization

plateau, followed by a 6-mins accelerated depolarization, and then a second plateau. Oxygen and

glucose deprivation-induced astrocyte Vm depolarization was only marginally (10%) inhibited by inhibition of ionotropic glutamate, c-aminobutyric acid, purinergic receptors, and glutamate transporters, suggesting increase in extracellular

[K+ ] was primarily responsible for the astrocytic Vm change. When glycolysis was inhibited the Vm depol was increased by 500%. The authors conclude that "Altogether, hippocampal astrocytes appear to be electrophysiologically more resistant to acute ischemia insults as compared with neurons, and this should allow astrocytes to rescue

endangered neurons in the face of acute ischemia insults via their various homeostatic functions."

 

Relevance: Medium

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600545a.pdf

 

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*5. Protective role of reactive astrocytes in brain ischemia

Li et al.

 

Sullysummary: This is a beautiful paper with 22 authors from Sweden, Belgium and the US. The authoris have transgenic mice deficient in GFAP (G-/-) vimenting (V-/-) or both (G+V-/-); these proteins are hallmarks of reactive astrocytosis. G-/- and V-/- animals had the same infarct volumes as WTs, but double knockouts had infarct volumes up to 3X those of WTs. These and other results lead the authors to conclude that reactive astrocytosis is neuroprotective in ischemia, although it will take a much more careful reading on my part to figure out how this squares with the paper's additional findings that double knockout animals also had less gliosis, better neural graft integration, and better regeneration than WTs. Moreover, no neurobehavioral outcomes are in evidence. The paper is relevant not only for its putative illustration of the role of astrocytes in ischemia, but also on JCBFM-worthy methods for MCAO.

 

Relevance: Medium

Link: http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600546a.pdf

 

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*6. Nitrite does not provide additional protection to thrombolysis in a rat model of stroke with delayed reperfusion

Schatlo et al.

 

Sullysummary: The authors, from the surgical neurology branch of NIH in Bethesda, demonstrate that, contrary to earlier reports, sodium nitrite (an NO donor) does not protect against rt-PA-induced reperfusion after focal ischemic stroke. That would be interesting enough, but this paper (again, to reiterate, from the NIH) gives us a roadmap for rational study design of neurprotection in focal ischemic stroke. In the discussion, the authors underscore (albeit implicitly) the importance of STAIR criteria in such studies. A couple of things to take home:

 

     1. It is in fact acceptable to present data in which thrombolysis has been simulated with filament MCAO + tPA. Based on this report and others I have read, the clot model of MCAO has no advantages and many disadvantages, and should go off and die.

 

     2. The use of older animals for this kind of research may be critical.

 

     3. Some animals were excluded from analysis. No big deal: state how many, and why, and then move the fuck on. I guess if you wanted to, you COULD just throw out the whole goddam data set and cripple your chances for publication. That's another option. But these guys--from NIH--just don't roll that way. Maybe there's a lesson in all that. Dunno.

 

     4. It is possible to publish negative results, provided that the findings are negative and well-controlled. Of course, it helps if you're actually FROM the NIH...

 

Relevance: HIGH

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600542a.pdf

 

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*7. Acute plasmalemma permeability and protracted clearance of injured cells after controlled cortical impact in mice.

Whalen, et al.

 

Sullysummary. The authors basically head-bonked mice and used propidium iodide to asses plasmalemma permeability. They found early permeability as a persistent feature of cell injury in cortex and hippocampus. The authors suggest that plasmalemma damage is a fundamental marker of cellular injury after CCI; some injured cells might have an extended window for potential rescue by neuroprotective strategies.

 

Relevance: Low.

Linke (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600544a.pdf

 

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*8. Plasminogen potentiates thrombin cytotoxicity and contributes to pathology of intracerebral hemorrhage in rats.

Fujimoto et al.

 

Sullysummary: The data presented suggests that the plasminogen/plasmin system enhances the neurotoxicity of thrombin in the setting of brain hemorrhage. Since t-PA is often administered for stroke, and since it activates plasminogen, and since its administration often causes hemorrhage, this should give advocates of stroke thrombolysis considerable pause. But whatever.

 

Relevance: Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600547a.pdf

 

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*9. Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion.

MacLellan, et al.

 

Relevance: Very Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600548a.pdf

 

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*10. Inducible nitric oxide synthase does not mediate brain damage after transient focal cerebral ischemia in mice.

Pruss, et al.

 

Sullysummary: This one is liable to shake a few trees. One of the shibboleths of current thinking about focal ischemia is that iNOS is a bad boy, contributing to inflammation (WBCs), oxidative stress (ONOO-), DNA damage and mitochondrial respiratory inhibition. The authors, in a technical tour de force that you should read just for the damn methods, basically crush this idea. No iNOS mRNA. No iNOS protein. No protection in iNOS-/- mice. No iNOS when dural inflammation is instigated by interleukins. The one concern I have about this study is the short ischemic interval: 45 mins or 60 mins. I need to do a second, more careful reading to see if I can pick up any other flaws, but, overall, I have to believe that JCBFM wouldn't take a paper with such a provocative conclusion (the title alone is going to make some people go all pale and trembly) if the data wasn't solid and the reviews weren't strong. Of course, this does nothing to knock down the idea that nNOS is bad for you (and, as it happens, directly connected to the glutamate receptor through PSD95).

 

Relevance: HIGH.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600550a.pdf

 

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*11. Autophagy is increased after traumatic brain injury in mice and is partially inhibited by the antioxidant

c-glutamylcysteinyl ethyl ester. Lai1, et al.

 

Sullysummary (verbatim): Autophagy is a homeostatic process for recycling of proteins and organelles, induced by nutrient deprivation and regulated by oxygen radicals. For a quickie review, see: http://en.wikipedia.org/wiki/Autophagy. We don't know how much of a role it plays in brain injury. The authors present data suggesting that autophagy occurs after experimental TBI, and that oxidative stress contributes to this process. No clues on correct pronunciation of "authophagy." Sorry.

 

Relevance: Lo.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600551a.pdf

 

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*12. Apolipoprotein D is elevated in oligodendrocytes in the peri-infarct region after experimental stroke: influence of enriched environment. Rickhag1, Wieloch, et al.

 

Sullysummary: Zees eez pehper from Sveden, yes? Ze investigators are eenterested in ze remodeling of ze injured brain and ze role of lipid trafficking, yes? Somehow, between trying to keep warm and maintaining their neutrality, these Swedes investigated the role of the well-characterized lipid trafficking protein apolipoprotein D. They found increased activity around the core of the infarct, and associated with oligos. Rats that were in a stimulating environment did better. I didn't read carefully enough to ascertain what the "stimulating" environment was. I can only assume this means the rats were transported outside of Sweden aften injury, or were exposed to members of the Swedish Female Olympic Swim Team during convalescence.

 

Relevance: Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600552a.pdf

 

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*13. DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats.

Yanagisawa, Kitamura1, Hiroshi, et al.

 

Sullysummary: Obviously an Irish paper. DJ-1 is the gene implicated in familial Parkinson's, and functions as an antioxidant, chaperone and transcriptional regulator. In this study, instrastriatal injection protected against ROS production and reduced infarct volumes in a rat MCAO model. The paper has relevance to us not only becuase of its findings but also for its methods.

 

Relevance: HIGH.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600553a.pdf

 

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*14. Comparison of plasma input and reference tissue models for analysing [11C]flumazenil studies. Klumpers, et al.

 

Relevance: Very low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600554a.pdf

 

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*15. The mechanisms of acute ischemic injury in the cell processes of developing white matter astrocytes. Salter et al.

 

 

Sullysummary. In an OGD model, the investigators show that injury results in loss of astrocytic processes and soma, particularly in white matter. They gave some stuff. In accordance with Krause's law, it seemed to help. Yawn.

 

Relevance: Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600555a.pdf

 

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*16. Lengthening the G1 phase of neural progenitor cells is concurrent with an increase of symmetric neuron generating division after stroke. Zhang et al.

 

Sullysummary: From our good buddy Mike Chopp over at Ford. I just LOVE THAT MAN. But not in a gay way. Adult rats were stroked and the cell cycle interrogated with BDU. Mike et al conclude that stroke triggers a shortening of the cell-cycle that expands the neuroprogenitor pool early on. Okay, sure. Then why don't our brains just grow back?

 

Relevance: Medium.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600556a.pdf

 

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*17. Neuronal HIF-1a protein and VEGFR-2 immunoreactivity in functionally related motor areas following a focal M1 infarct. Stowe1, et al.

 

Sullysummary: Not much to say. I was pretty underwhelmed.

 

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Relevance: Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600560a.pdf

 

*18. Acute astrocyte activation in brain detected by MRI: new insights into T1 hypointensity. Sibson et al.

 

Relevance: Very Low.

 

*19. The effect of labeling parameters on perfusion-based fMRI in nonhuman primates. Zappe, et al.

 

Relevance: Very Low.

Link (PDF): http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600564a.pdf

 

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END SUMMARY.