Deans' stroke musings: IL33 (Interleukin 33)/ST2 (Interleukin 1 Receptor-Like 1) Axis Drives Protective Microglial Responses and Promotes White Matter Integrity After 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.

Wednesday, April 28, 2021

IL33 (Interleukin 33)/ST2 (Interleukin 1 Receptor-Like 1) Axis Drives Protective Microglial Responses and Promotes White Matter Integrity After Stroke

WHOM is going to do the followup research in humans and create protocols that establish this benefit? Specific names only. With NO LEADERSHIP, nothing will occur.

IL33 (Interleukin 33)/ST2 (Interleukin 1 Receptor-Like 1) Axis Drives Protective Microglial Responses and Promotes White Matter Integrity After Stroke

Originally published27 Apr 2021https://doi.org/10.1161/STROKEAHA.120.032444Stroke. ;0:STROKEAHA.120.032444

Abstract

Background and Purpose:

Emerging evidence highlights the importance of IL33 (interleukin 33) and its receptor (ST2 [interleukin 1 receptor-like 1]) in normal brains and neurological disorders. This study explores the function of the IL33/ST2 signaling axis and a transcription factor STAT6 (signal transducer and activator of transcription 6) in white matter integrity and long-term recovery after stroke.

Methods:

Transient middle cerebral artery occlusion was induced in wild type, ST2 knockout, STAT6 knockout, and microglia/macrophage-depleted (by PLX5622 diet) mice. Sensorimotor and cognitive functions were evaluated. White matter integrity was measured by immunofluorescent staining, diffusion tensor imaging, electron microscopy, and electrophysiology. The death of oligodendrocytes and its precursor cells (OPC) and the microglia/macrophage responses were evaluated 3 days after stroke. Primary microglia-oligodendrocyte/OPC cocultures were used for mechanistic studies. Parametric tests (Student t test or ANOVA) or nonparametric Mann-Whitney U test were used for statistical analysis based on the numbers of groups, types of variables, and the structure of each data set.

Results:

ST2 deficiency exacerbates sensorimotor and cognitive deficits for 28 days after middle cerebral artery occlusion compared with wild-type mice, which was accompanied by deteriorated structural damages and impaired conduction of compound action potentials in white matter. ST2 knockout mice displayed increased death of oligodendrocytes and OPCs, and a concomitant exacerbation in neuroinflammation 3 days after stroke. Using microglia/macrophage-depleted mice and microglia-oligodendrocyte/OPC cocultures, we showed that IL33 protected oligodendrocytes and OPCs against ischemic injury in a microglia/macrophage dependent manner. Further mechanistic studies identified STAT6 as a molecule that mediates the protective effects of IL33/ST2 on oligodendrocytes in the ischemic brain. IL33 treatment failed to rescue oligodendrocytes and OPCs after stroke in STAT6 knockout mice.

Conclusions:

These results shed light on the IL33/ST2/STAT6 signaling as a potential immune regulatory mechanism to modulate microglia/macrophage activity, improve white matter integrity, and restore long-term neurological functions after stroke.