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.

Tuesday, March 23, 2021

Abstract P70: SPAK/OSR1 Signaling as a Novel Target for Post-Stroke Oxidative Stress Brain Injury

 So cultured mouse neurons were used. Your hospital is responsible for getting live mouse testing done and then human testing. Then distribute the created protocols worldwide.

Abstract P70: SPAK/OSR1 Signaling as a Novel Target for Post-Stroke Oxidative Stress Brain Injury

Originally publishedhttps://doi.org/10.1161/str.52.suppl_1.P70Stroke. 2021;52:AP70

Stroke is the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Currently, recombinant tissue plasminogen activator and endovascular thrombectomy are the two primary therapy strategies for acute ischemic stroke patients. Reactive oxygen species (ROS)-mediated oxidative stress can cause brain injury during reperfusion. We have shown that the Ste20/SPS1-related proline-alanine-rich protein kinase/oxidative stress-responsive kinase-1 (SPAK/OSR1) are activated in ischemic stroke brains, resulting in worsened outcomes in murine stroke models. SPAK activation induces the production of pro-inflammatory cytokines. Post-stroke administration of a novel SPAK inhibitor ZT-1a attenuates cerebral edema and protects against brain damage in in vivo model of ischemic stroke. However, whether ROS mediated oxidative stress directly activate SPAK/OSR1 pathway and induces SPAK pro-inflammatory cytokine production in ischemic brains remains unknown. In our extended study, we examined activation of SPAK/OSR1 and its substrate Na-K-Cl cotransporter (NKCC1) in cultured mouse primary neurons in response to hydrogen peroxide (H2O2)-mediated oxidative stress. We found that exposure of neurons to H2O2 for 24 hrs triggered upregulation of protein expression and phosphorylation activation of SPAK/OSR1 and NKCC1 (p < 0.05), which are accompanied with an increase in intracellular Na+ concentration and neuronal death (p < 0.01). These changes were blocked by an ROS scavenger ebselen. Interestingly, both novel SPAK inhibitor ZT-1a and NKCC1 inhibitor bumetanide are able to block H2O2-induced neuronal damage. We are in the process to assess effects of SPAK inhibitor ZT-1a in reducing ROS-mediated inflammation and brain injury in in vivo model of ischemic stroke. Together, our study suggests that ROS can activate SPAK/OSR1 complex during reperfusion injury and the therapeutic potentials of SPAK inhibitor ZT-1a for ischemic stroke.

 

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