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.

Thursday, February 5, 2026

New research shows improving blood flow to the brain in arteries with plaque did not improve cognitive skills

 Why would you even think that? With the Circle of Willis being complete there are four arteries feeding the brain, a miniscule improvement in one artery won't bring more oxygen to the brain. 

Doesn't ANYONE IN STROKE KNOW HOW TO THINK?

Proving once again we have blithering idiots in stroke! I would never do stenting or a carotid endarterectomy because of the possible bad consequences (i.e. stroke).

New research shows improving blood flow to the brain in arteries with plaque did not improve cognitive skills

Improving blood flow to the brain by opening a narrowed neck artery may not improve patients’ cognitive skills, according to a preliminary late-breaking science presentation at the American Stroke Association’s International Stroke Conference 2026

“Whether patients undergo a procedure to remove plaque in the carotid artery, known as a carotid endarterectomy, stenting to insert a flexible tube to hold open the narrowed part of the artery, or a combination of medications and lifestyle guidance without a procedure, there should be no expectation that cognition will improve after the treatment,” said study lead author Ronald M. Lazar, Ph.D., a professor of neurology at the University of Alabama at Birmingham and director of the UAB Evelyn F. McKnight Brain Institute

Carotid artery stenosis is a condition where the major blood vessels in the neck become narrowed, usually because of plaque buildup. Standard treatment focuses on strong medical therapy — such as aspirin to prevent blood clots, medicines to control blood pressure and cholesterol, and lifestyle changes like quitting smoking, being more active, eating a healthy diet and losing weight when needed. When the artery becomes severely narrowed, or more than 70 percent blocked, doctors may also recommend a procedure to reopen it, either through carotid endarterectomy or stenting.

The CREST‑2 Trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) compared how often strokes occurred in people who were randomly assigned to one of three groups: intensive medical therapy alone, medical therapy plus carotid endarterectomy or medical therapy plus stenting.

Earlier studies have generally shown that people with carotid stenosis tend to do worse on cognitive tests. To examine this more closely, CREST‑2 included a special “cognitive core” component. Participants completed cognitive testing before treatment and then once a year for up to four years. This was the first large randomized trial of carotid stenosis to include cognitive performance as a major outcome.

“The brain needs a steady flow of blood to get oxygen for its cells. When blood vessels can’t deliver enough blood, the brain doesn’t get enough oxygen, and the neurons can’t work properly, which impacts the brain’s ability to function properly. This often leads to changes in cognitive skills like attention, processing speed and decision-making skills,” Lazar said.

In 2021, Lazar and colleagues published results in Stroke, the journal of the American Stroke Association. They found that, before treatment, 786 patients in CREST‑2 with severe but symptom‑free carotid stenosis scored lower on cognitive tests — especially memory — compared with a separate group of people matched for age, sex and cardiovascular risk factors.

“The 2021 analysis indicated that revascularization might improve cognitive function,” said Lazar, who is the principal investigator of the Cognitive Core substudy and an overall co‑investigator for CREST‑2.

However, after an average of 2.8 years of follow‑up, the substudy found no meaningful differences in thinking or memory between people who had a procedure (stenting or surgery) and those who only received intensive medical therapy. “Even among participants with the lowest cognitive function at the start of the study, who were expected to gain the most from these treatments, there were still no differences in cognitive skills among the treatment groups,” Lazar said.

Participants who had a stroke during the study did show cognitive decline, confirming that the cognitive tests were sensitive enough to detect real changes in brain function.

These findings may influence how clinicians talk with patients about the potential benefits of surgery or stenting. 

“Health care professionals can no longer assert that treatment of carotid stenosis will improve cognition. However, worsening cognition over time may be a signal that treatment may need to be reevaluated and possibly adjusted,” Lazar said.

The study could not determine whether reduced blood flow alone explains cognitive decline in people with carotid artery disease. “Some characteristics of a blockage can cause small particles to travel to the brain. These particles may, over time, affect how the brain functions. This is an area we plan to explore in our future research,” Lazar said.

The study had limitations. All cognitive testing was done by phone, which meant researchers could not assess visuo‑spatial skills or the full range of executive functions like complex decision‑making. In addition, only English‑speaking participants were included, which means the results may not apply to people from other language or cultural backgrounds.

At UAB, Lazar holds the Evelyn F. McKnight Endowed Chair for Learning and Memory in Aging.

Stroke Trial Tips Scale Further to Favor Intra-Arterial Lytic After EVT

 This doesn't get you 100% recovered, so you're STILL APPROVING FAILURE AS A MATTER OF COURSE!

Stroke Trial Tips Scale Further to Favor Intra-Arterial Lytic After EVT

CHOICE-2 supports intra-arterial alteplase after successful reperfusion(Success is 100% recovery, quit trying to justify failure by using your tyranny of low expectations! Reperfusion is only the first step, what are the EXACT FOLLOWON STEPS TO 100% RECOVERY?)

NEW ORLEANS -- A stronger case could be made for intra-arterial (IA) alteplase after successful mechanical thrombectomy based on more randomized data, this time the CHOICE-2 trial from Spain.

In acute ischemic stroke patients with large vessel occlusions who achieved majority-complete reperfusion with endovascular therapy (EVT), adjunctive IA alteplase further increased the likelihood of good functional outcomes when given in the 24-hour window. Ninety-day modified Rankin Scale (mRS) scores of 0-1 were significantly more likely after alteplase treatment compared with EVT alone (57.5% vs 42.9%, P=0.002).

Moreover, alteplase improved the secondary outcomes of CT perfusion and patient-reported quality of life.

"Let me announce happily that CHOICE-2 is a positive clinical trial," said Ángel Chamorro, MD, PhD, of the University of Barcelona and Hospital Clinic of Barcelona, to applause at the International Stroke Conference.

With the number needed to treat being seven patients, "let me remind you that this is approximately the number needed to treat patients with IV thrombolysis within 3 hours from the onset of symptoms, compared to placebo. So I think this is a remarkable figure," he added.

As for the safety of IA alteplase, the results were mixed: no excess symptomatic intracerebral hemorrhage was detected at 36 hours (1.4% vs 0.5% for controls, P=0.33), but death at 90 days was significantly more likely in the treated group (12.1% vs 6.4%, P=0.04).

Chamorro argued that the apparent difference in mortality likely reflects an "extremely low" event rate among control patients in CHOICE-2. Indeed, in the older PEARL trial, all-cause mortality occurred in 17.1% of patients who received adjunctive IA alteplase and 11.3% of those who received EVT alone, a nonsignificant difference.

The benefit of using adjunctive IA thrombolytics is based on frequent observations that EVT patients often still have functional impairments; lingering microvascular hypoperfusion is believed to be the culprit.

The original CHOICE trial had been stopped early due to a shortage of the placebo, Chamorro said. However, it did suggest benefit with IA alteplase for stroke patients with successful angiographic reperfusion: there was an improvement in the mRS score at 90 days with alteplase 0.225 mg/kg, maximum 22.5 mg (a slightly different dose to CHOICE-2's maximum 20 mg over a 15-minute infusion).

More recently, promising results have been reported with clot-busters after successful EVT, namely IA tenecteplase in ANGEL-TNK and IA alteplase in PEARL, both presented last year. However, there's also been disappointing results in the POST-TNK and POST-UK trials in which adjunctive IA tenecteplase and urokinase, respectively, fell short in achieving longer survival without disability after EVT.

American stroke guidelines, updated last week, thus state that adjunctive IA thrombolytics with urokinase, alteplase, or tenecteplase "may be reasonable" to improve cerebral reperfusion and 90-day functional outcomes in stroke patients with complete or near-complete EVT (class IIb recommendation).

"The usefulness of administration of adjunctive intra-arterial thrombolytics, namely urokinase and tenecteplase, after successful thrombectomy remains uncertain, as data from four major [randomized controlled trials] are conflicting," the guideline authors reasoned.

The open-label CHOICE-2 trial was conducted at 14 Spanish centers with blinded assessment of clinical and imaging outcomes.

The study included stroke patients with large vessel occlusions with majority-complete reperfusion (expanded Thrombolysis in Cerebral Infarction grade [eTICI] 2b50-3) post-EVT who had been treated within 24 hours of stroke onset. The Alberta Stroke Program Early CT Score (ASPECTS) could not be below 6, and patients were excluded if they had an NIH Stroke Score of 25 or higher or if they had contraindications to alteplase.

Ultimately, 440 participants were randomized to EVT alone or with IA alteplase. The median cohort age was around 76 years, and the group was roughly split between the sexes. Median NIH Stroke Score was 15, about 64% had a preceding IV thrombolysis, and cause of stroke was cardioembolic in nearly half of cases.

Egypt’s Ismailia Medical Complex awarded WSO Diamond Status for stroke care

 

'Care' is NOT RECOVERY!

This is the whole problem in stroke enumerated in one word; 'care'; NOT RECOVERY! 

Our non-existent stroke leadership should be demanding RECOVERY NOT 'CARE'! This is you, WSO!

My god, anyone in the business world would be fired immediately for managing or caring about something rather than delivering RESULTS. And this is why this is a complete fucking failure! This does nothing to guarantee recovery for survivors!

If your stroke medical 'professional'/hospital is touting 'care' it means they are a failure because they are delivering 'care'; NOT RECOVERY! I would never go to a failed hospital! Anytime I see the word 'care' associated with a stroke hospital; I immediately think fucking failure!

YOU have to get involved and change this failure mindset of 'care' to 100% RECOVERY! Survivors want RECOVERY, NOT 'CARE'!

I see nothing here that states going for 100% recovery! You need to create EXACT PROTOCOLS FOR THAT!

ASK SURVIVORS WHAT THEY WANT, THEY'LL NEVER RESPOND 'CARE'! This tyranny of low expectations has to be completely rooted out of any stroke conversation! I wouldn't go there because of such incompetency as not having 100% recovery protocols!

RECOVERY IS THE ONLY GOAL IN STROKE!

GET THERE!

Egypt’s Ismailia Medical Complex awarded WSO Diamond Status for stroke care

Egypt’s Ismailia Medical Complex has been awarded Diamond Status for stroke care by the World Stroke Organization, recognising its performance in emergency stroke treatment, the General Healthcare Authority (GHA) said.

_
Photo courtesy of Egypt's cabinet

 

The Diamond designation, the highest tier under the Angels Awards for the fourth quarter of 2025, places the complex among a limited number of stroke centres worldwide meeting top international benchmarks for diagnosis speed, treatment quality, and patient outcomes.

According to the GHA, the hospital treats more than 40 stroke emergencies a day and has delivered over six million medical services since it began operating.

GHA chairman Ahmed El-Sobky said the complex has recorded improvements in key clinical indicators, including an increase in arterial recanalization rates from 25 percent to 31 percent, reflecting faster intervention and improved acute stroke care.

He said the stroke unit operates alongside a 24-hour neuro-interventional catheterization service, allowing immediate treatment of cerebral haemorrhage, aneurysms, and vascular blockages. Post-stroke care is provided through 10 specialized outpatient clinics each week, offering follow-up and rehabilitation services.

 

Official figures show the complex has provided over 6 million services, including 850,000 emergency cases, 1.5 million outpatient visits, 3.9 million diagnostic and laboratory tests, and more than 82,000 surgical procedures since opening.

El-Sobky said the Ismailia Medical Complex is the first facility in Egypt to receive accreditation from both the General Authority for Healthcare Accreditation and Regulation (GAHAR) and the Joint Commission International (JCI). Its laboratories are ISO-certified, while its stroke unit holds direct accreditation from the World Stroke Organization.

The Angels Awards assess stroke centres worldwide based on performance indicators, including diagnosis speed, treatment effectiveness, adherence to clinical guidelines, and patient outcomes.

Diamond Status represents the highest level of recognition, awarded to facilities that demonstrate consistently strong performance across emergency response, intensive care, and post-stroke rehabilitation.

The programme, run by the World Stroke Organization in partnership with international stroke-care initiatives, evaluates centres every quarter using measurable criteria such as door-to-imaging time, door-to-needle time, use of reperfusion therapies, and compliance with evidence-based treatment pathways.

ISC26 Draws More Than 5,000 Global Stroke Experts

And NONE OF THESE 'EXPERTS' are working on 100% recovery! Totally ignoring what survivors want! Hope they all get their comeuppance when they are the 1 in 4 per WHO that has a stroke? Then you just might want 100% recovery. Scream at these blithering idiots for putting any limit on your recovery.  

Let's see how long this conference has been TOTALLY FUCKING INCOMPETENT!

  • International Stroke Conference (30 posts to February 2014) And I'm sure much much earlier than that!
  •  ISC26 Draws More Than 5,000 Global Stroke Experts

    NEW ORLEANS – More than 5,000 medical professionals are in New Orleans for the American Stroke Association International Stroke Conference 2026 (ISC26) which started on Feb. 4 and runs for three days. Taking place at the New Orleans Ernest N. Morial Convention Center, ISC26 is the world’s premier scientific meeting focused exclusively on stroke

    Rosmarinic Acid Alleviates Ischemic Stroke by Targeting BAG3 to Modulate Autophagy via the P62-Keap1-Nrf2 Pathway

     Comments are embedded in the research.

    Rosmarinic Acid Alleviates Ischemic Stroke by Targeting BAG3 to Modulate Autophagy via the P62-Keap1-Nrf2 Pathway


    https://doi.org/10.1016/j.phymed.2026.157904Get rights and content

    Abstract

    Ischemic stroke remains a major clinical challenge due to limited treatment options and the lack of effective neuroprotectants(Meaning they don't know how to stop the neuronal cascade of death the first week.  Thus letting hundreds of millions of neurons to continue to die!). Here, we identified a novel neuroprotective(We will never get any urgency as long as we still call it neuroprotection rather than the neuronal cascade of death. Which term suggests urgency to lay people?)

    mechanism of rosmarinic acid (RosA), a natural phenolic compound, through precision targeting of the autophagy regulator BAG3. Using activity-based protein profiling, we demonstrated that RosA covalently bound to the Cys378 residue of BAG3, disrupting its interaction with the selective autophagy receptor P62. This disruption activated the P62/Keap1/Nrf2 signaling axis, attenuating excessive autophagic flux and reducing neuronal injury. Both in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) and in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) models confirmed that RosA significantly reduced autophagosome accumulation, infarct volume, and neurological deficits in a BAG3-dependent manner. BAG3 knockdown mimicked RosA’s effects and abolished RosA-induced autophagy regulation, highlighting BAG3 as the functional target. These findings not only elucidated the molecular mechanism of RosA but also proposed BAG3 as a promising therapeutic target for ischemic stroke intervention.

    Introduction

    Globally, ischemic stroke stands as a critical neurological emergency, notable for its widespread occurrence and severe repercussions, including elevated mortality and persistent functional deficits(Jolugbo and Ariens, 2021, Wang et al., 2024b). The increasing prevalence of ischemic stroke is largely driven by an aging global population and the rise in lifestyle-related risk factors, with more than 13 million new cases reported annually(Saini et al., 2021). Current clinical interventions primarily aim to restore cerebral blood flow, chiefly involving intravenous recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis or endovascular clot retrieval to reinstate cerebral perfusion(Tsivgoulis et al., 2023, Cui et al., 2024). Despite its exclusive FDA approval status among thrombolytics, rt-PA therapy faces dual constraints: narrow therapeutic window (≤4.5 hours post-onset) and significant risks including cerebral hemorrhage and reperfusion-related damage(Arkelius et al., 2024). Neuroprotective agents, including non-competitive NMDA receptor antagonists (e.g., memantine) and free radical scavengers (e.g., Ebselen), have demonstrated limited clinical success due to adverse effects, inadequate blood-brain barrier penetration, narrow therapeutic window, and off-target effects(Zhang et al., 2024, Narayan et al., 2021). These challenges highlight the pressing need for safer, more effective therapeutic strategies for ischemic stroke.
    The development of cerebral ischemia triggers an intricate sequence of molecular and cellular perturbations, including ionic imbalance, energy depletion, excitotoxicity, oxidative stress, inflammatory responses, blood-brain barrier disruption, and autophagy dysregulation(Qin et al., 2022). Emerging research implicates autophagic processes as key modulators of ischemic stroke pathogenesis(Shi et al., 2023). This primordial self-renewal pathway, executed through lysosomal processing of cellular constituents, forms an indispensable biological infrastructure for sustaining functional stability. Recent studies have shown that ischemic stress dynamically modulates autophagic flux, with moderate activation of autophagy exerting cytoprotective effects by clearing damaged organelles and misfolded proteins during the early phase of ischemia(Hou et al., 2019). However, prolonged energy deprivation can convert this adaptive process into a detrimental one, wherein excessive autophagosome accumulation overwhelms lysosomal degradation capacity, ultimately leading to cellular damage(Hou et al., 2019, Mo et al., 2020). Studies indicate that moderate autophagy participates in reparative processes such as neurogenesis and synaptic plasticity, whereas excessive autophagy can lead to neuronal death(Ajoolabady et al., 2021). Therefore, targeting autophagy regulation holds promise not only for "life-saving" effects in the acute phase but also for long-term "repair promotion." Modulating autophagy shows promise in protecting neurons and potentially extending the therapeutic window. Currently, pharmacological interventions targeting autophagy pathways (e.g., Rapamycin, 3-MA, NCOA4 inhibitors) and natural compounds (e.g., Ginkgolide B, HSYA) have demonstrated therapeutic potential by fine-tuning autophagic activity(Wu et al., 2025). Clinical studies have reported elevated LC3-II/LC3-I ratios and decreased P62 levels in the serum of stroke patients, correlating with infarct size and unfavorable clinical outcomes(Wang et al., 2024a). Furthermore, experimental studies demonstrate that neuronal death and brain injury are alleviated in both cellular and animal models of ischemic stroke through pharmacological autophagy inhibition or genetic knockdown of critical autophagy mediators such as Beclin1 and ATG7. Additionally, triolein has been shown to mitigate ischemic injury by suppressing autophagy and inflammation via activation of the AKT/mTOR signaling pathway(Wang et al., 2024a). Collectively, these observations position the autophagy-lysosomal system as a viable therapeutic target for stroke intervention.
    Traditional Chinese Medicine (TCM) and polyphenolic natural products represent a largely underexplored reservoir of neuroprotective agents for ischemic stroke, offering multi-target mechanisms that align well with the disease’s complex pathophysiology(Abdelsalam et al., 2023). Polyphenols, including epigallocatechin gallate (EGCG) and salvianolic acid B (Sal B), exhibit neuroprotective effects in cerebral ischemia by targeting multiple pathological pathways, such as attenuating ROS-mediated damage, suppressing neuroinflammatory cascades, and restoring mitochondrial bioenergetics(Park et al., 2024, Guo et al., 2022). Among these, rosmarinic acid (RosA), abundantly present in Salvia rosmarinus Spenn., has attracted significant attention due to its pleiotropic biological activities. A network pharmacology study has identified seven active compounds (RosA, chlorogenic acid, ferulic acid, Sal B, caffeic acid, (Z)-ligustilide, and tanshinone IIA), five core molecular targets (TNF-α, IL-1β, AKT, BCL2, and CASP3), and four key signaling pathways involved in the treatment of ischemic stroke(Pang et al., 2024). RosA has been reported to alleviate post-stroke depression in rats following transient focal cerebral ischemia by enhancing antioxidant defenses(Wang et al., 2021). In addition, RosA exerts neuroprotective effects through activation of the Nrf2 and HO-1 signaling pathways(Xu et al., 2021). Mechanistic studies further show that RosA attenuates cerebral injury and cognitive deficits in permanent MCAO-induced ischemic stroke, primarily through enhancing neuronal synaptic transmission, reducing inflammatory processes, and boosting brain-derived neurotrophic factor (BDNF) levels(Xu et al., 2021). Studies have confirmed that RosA exerts multiple effects in autophagy regulation. For instance, it can enhance autophagy by targeting to hepatocyte nuclear factor 4α (HNF4α)(Chen et al., 2025), activate the JAK2/STAT3/CTSC pathway to restore autophagic flux and lysosomal function(Luo et al., 2024), and regulate the phosphorylation level of ERK1/2 to modulate autophagy(Sengelen and Onay-Ucar, 2024). However, most current studies focus on its downstream signaling pathways or indirect target molecules, and the direct molecular targets of RosA in ischemic stroke remain unclear.
    In this study, we demonstrated that RosA exerted neuroprotective effects following ischemic stroke in both in vitro and in vivo models. Utilizing a chemoproteomics approach, we designed a clickable RosA probe (RosA-p) and identified Bcl-2-associated athanogene 3 (BAG3) as a direct covalent target of RosA through activity-based protein profiling (ABPP) and cellular thermal shift assays (CETSA). BAG3 is a crucial autophagic adapter protein(Liu et al., 2023b, Sweeney et al., 2024). However, it remains unclear whether RosA can affect the autophagic process by binding to BAG3, regulating the expression or activity of BAG3. Elucidating this interaction represents a significant innovative aspect of this study. Our findings revealed that RosA covalently bound to cysteine 378 (Cys378) of BAG3 via Michael addition, thereby disrupting its interaction with the autophagy receptor P62. This interaction activated the P62/Keap1/Nrf2 signaling axis, leading to the suppression of autophagy and a reduction of cerebral infarction in ischemic stroke mice. Importantly, neuron-specific knockdown of BAG3 abolished the therapeutic effects of RosA, confirming BAG3 as a key mediator of RosA’s neuroprotective activity. These findings not only supported the therapeutic potential of RosA as a novel neuroprotectant but also validated BAG3 as a druggable target for ischemic stroke, offering a promising strategy for modulating autophagy in cerebrovascular disease.

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