Deans' stroke musings: Post-stroke hippocampal neurogenesis is impaired by microvascular dysfunction and PI3K signaling in cerebral amyloid angiopathy

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.

Sunday, October 13, 2024

Post-stroke hippocampal neurogenesis is impaired by microvascular dysfunction and PI3K signaling in cerebral amyloid angiopathy

What is your competent? doctor doing to get this tested and solved for in humans? Nothing? Like Usual? So you don't have a functioning stroke doctor, do you?

Post-stroke hippocampal neurogenesis is impaired by microvascular dysfunction and PI3K signaling in cerebral amyloid angiopathy

Olivia M. Osborne¹ omo17@miami.edu ∙ Manav Daftari¹ ∙ Oandy Naranjo¹ ∙ … ∙ Anthony J. Griswold^9,10 ∙ Derek M. Dykxhoorn^9,10 ∙ Michal Toborek^1,11 mtoborek@med.miami.edu … Show more

Highlights

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Function and tissue recovery after ischemic stroke are significantly impaired in 5xFAD mice

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Changes in the BBB reduce blood flow and reperfusion capability in the 5xFAD genotype

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Transcriptomic analysis links endothelial cells and hippocampal NPCs via the PI3K pathway

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Activation of the PI3K pathway rescues neurogenesis in 5xFAD mice post stroke

Summary

Ischemic stroke and cerebral amyloid angiopathy (CAA) pose significant challenges in an aging population, particularly in post-stroke recovery. Using the 5xFAD mouse model, we explore the relationship between CAA, ischemic stroke, and tissue recovery. We hypothesize that amyloid-beta accumulation worsens stroke outcomes by inducing blood-brain barrier (BBB) dysfunction, leading to impaired neurogenesis. Our findings show that CAA exacerbates stroke outcomes, with mice exhibiting constricted BBB microvessels, reduced cerebral blood flow, and impaired tissue recovery. Transcriptional analysis shows that endothelial cells and neural progenitor cells (NPCs) in the hippocampus exhibit differential gene expression in response to CAA and stroke, specifically targeting the phosphatidylinositol 3-kinase (PI3K) pathway. In vitro experiments with human NPCs validate these findings, showing that disruption of the CXCL12-PIK3C2A-CREB3L2 axis impairs neurogenesis. Notably, PI3K pathway activation restores neurogenesis, highlighting a potential therapeutic approach. These results suggest that CAA combined with stroke induces microvascular dysfunction and aberrant neurogenesis through this specific pathway.