Deans' stroke musings: KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury

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, April 9, 2024

KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury

Ask your competent? doctor if anything here is worth exploring for stroke recovery. DO NOT ACCEPT ANY ANSWER LESS THAN: 'We'll look into it by contacting researchers for more research.'! Not doing that is a complete sign of incompetence!

KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury

DOI:https://doi.org/10.1016/j.stem.2024.03.004

Highlights

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Mechanically injured organoids display hallmark features of traumatic brain injury
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TDP-43 dysfunction is a key driver of acute injury and is enhanced in ALS/FTD
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A CRISPRi screen identifies KCNJ2 inhibition as a therapeutic target in vitro
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Kcnj2 knockdown in mice reduces TDP-43 pathology and is protective against brain injury

Summary

Traumatic brain injury (TBI) strongly correlates with neurodegenerative disease. However, it remains unclear which neurodegenerative mechanisms are intrinsic to the brain and which strategies most potently mitigate these processes. We developed a high-intensity ultrasound platform to inflict mechanical injury to induced pluripotent stem cell (iPSC)-derived cortical organoids. Mechanically injured organoids elicit classic hallmarks of TBI, including neuronal death, tau phosphorylation, and TDP-43 nuclear egress. We found that deep-layer neurons were particularly vulnerable to injury and that TDP-43 proteinopathy promotes cell death. Injured organoids derived from C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) patients displayed exacerbated TDP-43 dysfunction. Using genome-wide CRISPR interference screening, we identified a mechanosensory channel, KCNJ2, whose inhibition potently mitigated neurodegenerative processes in vitro and in vivo, including in C9ORF72 ALS/FTD organoids. Thus, targeting KCNJ2 may reduce acute neuronal death after brain injury, and we present a scalable, genetically flexible cerebral organoid model that may enable the identification of additional modifiers of mechanical stress.