Journal Club for June 2009

Our new format includes only relevant articles. If you have articles that you believe should be included in the online journal club, send them to me before the 20th of the month. Journal club has been iffy lately because of all the work that’s going on; we are trying to catch up.

*1. MONDAY JOURNAL CLUB ARTICLE: The endogenous inhibitor of Akt, CTMP, is critical to ischemia-induced neuronal death. Nat Neurosci. 2009 May;12(5):618-26.

A key paper for us that may explain many of the discrepancies that drove us mad when we were doing our own Akt work. The upshot: Akt phosphorylation does not necessarily equate with Akt activation Herew the authors use a rat global brain ischemia model to show that (1) ischemia promotes marked phosphorylation and translocation of the pro-survival kinase Akt in CA1 neurons destined to die; (2) preconditioning, but not ischemia, promotes Akt kinase activity and phosphorylation of Akt targets; (3) ischemia promotes the expression of an endogenous Akt inhibitor, CTMP, and also promotes assemply of an Akt-CTMP complex in CA1; (4) CTMP is critical to ischemia induced neuronal death. Silencing of CTMP with RNAi allowed vulnerable cells in the CA1 to survive by disinhibiting Akt. An important and well-done paper with beautiful techniques and an elegant progression of experiments. Presented at Monday journal club by Sully.

Link (PDF): http://www.nature.com/neuro/journal/v12/n5/pdf/nn.2299.pdf

*2. The neuroprotective effect of prostaglandin E2 EP1 receptor inhibition has a wide therapeutic window, is sustained in time and is not sexually dimorphic. Takato Abe, et al.

A unisex neuroprotectant! Works in girls AND boys! This paper is primarily of interest for its methods. They're using an 80% reduction in LDF through the parietal bone as their threshold, which seems pretty rigorous. Their method of infarct volume measurement was--get this!--CRESYL VIOLET. Stroke volumes were reported graphically-numerically; the authors didn't include any of those cute little photomontages which seem to be _de rigeur_ for focal ischemia studies. Interesting. Also, I note that they removed the Lin correction for edema after 14 days, which is something that we need to think about. No MRI data.