Deans' stroke musings: A master regulatory network restoring brain glutamate homeostasis is coordinately activated in stroke

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Wednesday, January 17, 2018

A master regulatory network restoring brain glutamate homeostasis is coordinately activated in stroke

Somewhere in these 29 pages something might be useful. Which our great stroke association would analyze and distribute worldwide. Because right now your doctor and stroke hospital are not updating their stroke recovery protocols at all. https://www.biorxiv.org/content/biorxiv/early/2018/01/10/245928.full.pdf Mariko Kobayashi1,3, Corey Anderson2, Corinne Benakis2, Michael J. Moore1, Aldo Mele1, John J. Fak1, Christopher Y. Park1, Ping Zhou2, Josef Anrather2, Costantino Iadecola2, Robert B. Darnell1,3. 1Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. 2Fell Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY, 10065, USA. 3Correspondence: mkobayashi@rockefeller.edu, darnelr@rockefeller.edu
ABSTRACT
Altered miRNA expression in various disease states have been identified, but their global targets contributing to the collective regulatory power to promote or attenuate pathology remains poorly defined. Here we applied a combination of hi-throughput RNA profiling techniques, including AGO CLIP, miRNAseq, RNAseq and ribosomal profiling, to develop an unbiased and comprehensive view of miRNA:mRNA functional interactions following ischemia/reperfusion (IR) injury in the mouse brain. Upon acute I/R insult miR-29 family members were most prominently lost, with corresponding de-regulation of their global target sites. This leads to a dynamic, cascading mode of miR-29 target transcript activation, orchestrated by an initial translational activation and subsequent increase in target mRNA levels. Unexpectedly, activated genes include factors essential for glutamate signaling and reuptake, indicating a fundamental role for this regulatory network in modulating criticalendogenous neuroprotective programs to restore brain homeostasis. We integrated this data with human brain AGO CLIP profiles to infer target site variants that determine miRNA binding and to explore the role of non-coding site polymorphisms in stroke. Together these results establish a new strategy for understanding RNA regulatory networks in complex neurological disease.