Deans' stroke musings: Myeloperoxidase inhibition increases neurogenesis after ischemic 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.

Friday, August 26, 2016

Myeloperoxidase inhibition increases neurogenesis after ischemic stroke

What protocol does your doctor have to increase your neurogenesis? How does s/he know that neurogenesis is working? Does your doctor know ONE DAMN THING ABOUT NEUROGENESIS?
http://jpet.aspetjournals.org/content/early/2016/08/22/jpet.116.235127.abstract

+ Author Affiliations

¹ MGH;
² Massachusetts General Hospital

↵^*Address correspondence to: jwchen@mgh.harvard.edu

Abstract

The relationship between inflammation and neurogenesis in stroke is currently not well understood. Focal ischemia enhances cell proliferation and neurogenesis in the neurogenic regions including the subventricular zone (SVZ), dentate gyrus (DG) as well as non-neurogenic striatum, cortex in the ischemic hemisphere. Myeloperoxidase (MPO) is a potent oxidizing enzyme secreted during inflammation by activated leukocytes and its enzymatic activity is highly elevated after stroke. In this study, we investigated whether inhibition of MPO activity by a specific irreversible inhibitor, 4-aminobenzoic acid hydrazide (ABAH) or MPO-/- mice can increase neurogenesis after transient middle cerebral artery occlusion (tMCAO) in mice. ABAH administration increased the number of proliferating 5-bromo-2' deoxyuridine (BrdU)-positive cells expressing markers for neural stems cells, astrocytes, neuroprogenitors (Nestin), and neuroblasts (doublecortin) in the ischemic SVZ, anterior SVZ (aSVZ), striatum and cortex. MPO inhibition also increased levels of brain-derived neurotrophic factor (BDNF), phospho-cAMP response element-binding protein (pCREB Ser133), acetylated H3 (AcH3), and NeuN to promote neurogenesis in the ischemic SVZ. ABAH treatment also increased chemokine CXC receptor 4 (CXCR 4) expression in the ischemic SVZ. MPO-deficient mice treated with vehicle or ABAH both showed similar effects on the number of BrdU+ cells in the ischemic hemisphere, demonstrating that ABAH is specific to MPO. Taken together, our results underscore a detrimental role of MPO activity to post-ischemia neurogenesis and that a strategy to inhibit MPO activity can increase cell proliferation and improve neurogenesis after ischemic stroke.