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.

Monday, March 19, 2012

Coupling hippocampal neurogenesis to brain pH through pro-neurogenic small-molecules that regulate proton sensing G protein-coupled receptors

Someone smarter that me needs to reduce this to 8th grade level.
http://pubs.acs.org/doi/abs/10.1021/cn300025a

Abstract

Acidosis, a critical aspect of central nervous system (CNS) pathophysiology and a metabolic corollary of the hypoxic stem cell niche, could be an expedient trigger for hippocampal neurogenesis and brain repair. We recently tracked the function of our isoxazole stem cell-modulator small-molecules (Isx) through a chemical biology-target discovery strategy to GPR68, a proton (pH) sensing G protein-coupled receptor with no known function in brain. Isx and GPR68 co-regulated neuronal target genes like Bex1 (brain-enriched X-linked protein-1) in hippocampal neural progenitors (HCN cells), which further amplified GPR68 signaling by producing metabolic acid in response to Isx. To evaluate this pro-neurogenic small-molecule/proton signaling circuit in vivo, we explored GPR68 and BEX1 expression in brain and probed brain function with Isx. We localized proton-sensing GPR68 to radial processes of hippocampal type 1-neural stem cells (NSCs) and, conversely, localized BEX1 to neurons. At the transcriptome level, Isx demonstrated unrivaled pro-neurogenic activity in primary hippocampal NSC cultures. In vivo, Isx pharmacologically targeted type 1-NSCs, promoting neurogenesis in young mice, depleting the progenitor pool without adversely affecting hippocampal learning and memory function. After traumatic brain injury, cerebral cortical astrocytes abundantly expressed GPR68, suggesting an additional role for proton-GPCR signaling in reactive astrogliosis. Thus, probing a novel pro-neurogenic synthetic small-molecule’s mechanism-of-action, candidate target and pharmacological activity, we identified a new GPR68 regulatory pathway for integrating neural stem and astroglial cell functions with brain pH.

1 comment:

  1. Sure, I will, I wrote the paper! Basically, this paper reports that specific brain cells, including neural stem cells, have receptors to monitor the pH (acidity) of their environment. Low pH, as occurs with injury like stroke or trauma, or even cardiovascular exercise, which causes lactic acidosis, stimulates neurogenesis -- the production of new neurons. This could provide a very simple mechanistic link between exercise and hippocampal neurogenesis. The proton could be a simple trigger for production of new brain cells. This has important implications for exercise-jocks and for patients with brain disease.
    That's it in a nutshell.
    --Jay

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